Novel replisome-associated proteins at cellular replication forks in EBV-transformed B lymphocytes
Identifieur interne : 000D25 ( Ncbi/Merge ); précédent : 000D24; suivant : 000D26Novel replisome-associated proteins at cellular replication forks in EBV-transformed B lymphocytes
Auteurs : Huanzhou Xu [États-Unis] ; Ramon D. Perez ; Tiffany R. Frey [États-Unis] ; Eric M. Burton [États-Unis] ; Sudha Mannemuddhu [États-Unis] ; John D. Haley [États-Unis] ; Michael T. Mcintosh [États-Unis] ; Sumita Bhaduri-Mcintosh [États-Unis]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2019.
Abstract
Epstein-Barr virus (EBV) is an oncogenic herpesvirus and WHO class 1 carcinogen that resides in B lymphocytes of nearly all humans. While silent in most, EBV can cause endemic Burkitt lymphoma in children and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. The pathogenesis of such lymphomas is multifactorial but to a large extent depends on EBV’s ability to aggressively drive cellular DNA replication and B cell proliferation despite cell-intrinsic barriers to replication. One such barrier is oncogenic replication stress which hinders the progression of DNA replication forks. To understand how EBV successfully overcomes replication stress, we examined cellular replication forks in EBV-transformed B cells using iPOND (isolation of Proteins on Nascent DNA)-mass spectrometry and identified several cellular proteins that had not previously been linked to DNA replication. Of eight candidate replisome-associated proteins that we validated at forks in EBV-transformed cells and Burkitt lymphoma-derived cells, three zinc finger proteins (ZFPs) were upregulated early in B cells newly-infected with EBV in culture as well as expressed at high levels in EBV-infected B blasts in the blood of immunocompromised transplant recipients. Expressed highly in S- and G2-phase cells, knockdown of each ZFP resulted in stalling of proliferating cells in the S-phase, cleavage of caspase 3, and cell death. These proteins, newly-identified at replication forks of EBV-transformed and Burkitt lymphoma cells therefore contribute to cell survival and cell cycle progression, and represent novel targets for intervention of EBV-lymphomas while simultaneously offering a window into how the replication machinery may be similarly modified in other cancers.
Url:
DOI: 10.1371/journal.ppat.1008228
PubMed: 31841561
PubMed Central: 6936862
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Haley</name><affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>Department of Pathology and Stony Brook Proteomics Center, Stony Brook University, Stony Brook, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Stony Brook Proteomics Center, Stony Brook University, Stony Brook, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Mcintosh, Michael T" sort="Mcintosh, Michael T" uniqKey="Mcintosh M" first="Michael T." last="Mcintosh">Michael T. Mcintosh</name><affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Child Health Research Institute, Department of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Child Health Research Institute, Department of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Bhaduri Mcintosh, Sumita" sort="Bhaduri Mcintosh, Sumita" uniqKey="Bhaduri Mcintosh S" first="Sumita" last="Bhaduri-Mcintosh">Sumita Bhaduri-Mcintosh</name><affiliation wicri:level="2"><nlm:aff id="aff006"><addr-line>Division of Infectious Disease, Departments of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Infectious Disease, Departments of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Epstein-Barr virus (EBV) is an oncogenic herpesvirus and WHO class 1 carcinogen that resides in B lymphocytes of nearly all humans. While silent in most, EBV can cause endemic Burkitt lymphoma in children and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. The pathogenesis of such lymphomas is multifactorial but to a large extent depends on EBV’s ability to aggressively drive cellular DNA replication and B cell proliferation despite cell-intrinsic barriers to replication. One such barrier is oncogenic replication stress which hinders the progression of DNA replication forks. To understand how EBV successfully overcomes replication stress, we examined cellular replication forks in EBV-transformed B cells using iPOND (isolation of Proteins on Nascent DNA)-mass spectrometry and identified several cellular proteins that had not previously been linked to DNA replication. Of eight candidate replisome-associated proteins that we validated at forks in EBV-transformed cells and Burkitt lymphoma-derived cells, three zinc finger proteins (ZFPs) were upregulated early in B cells newly-infected with EBV in culture as well as expressed at high levels in EBV-infected B blasts in the blood of immunocompromised transplant recipients. Expressed highly in S- and G2-phase cells, knockdown of each ZFP resulted in stalling of proliferating cells in the S-phase, cleavage of caspase 3, and cell death. These proteins, newly-identified at replication forks of EBV-transformed and Burkitt lymphoma cells therefore contribute to cell survival and cell cycle progression, and represent novel targets for intervention of EBV-lymphomas while simultaneously offering a window into how the replication machinery may be similarly modified in other cancers.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gottschalk, S" uniqKey="Gottschalk S">S Gottschalk</name></author><author><name sortKey="Rooney, Cm" uniqKey="Rooney C">CM Rooney</name></author><author><name sortKey="Heslop, He" uniqKey="Heslop H">HE Heslop</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Allen, Ud" uniqKey="Allen U">UD Allen</name></author><author><name sortKey="Preiksaitis, Jk" uniqKey="Preiksaitis J">JK Preiksaitis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crombie, Jl" uniqKey="Crombie J">JL Crombie</name></author><author><name sortKey="Lacasce, As" uniqKey="Lacasce A">AS LaCasce</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Styczynski, J" uniqKey="Styczynski J">J Styczynski</name></author><author><name sortKey="Einsele, H" uniqKey="Einsele H">H Einsele</name></author><author><name sortKey="Gil, L" uniqKey="Gil L">L Gil</name></author><author><name sortKey="Ljungman, P" uniqKey="Ljungman P">P Ljungman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Mansour, Z" uniqKey="Al Mansour Z">Z Al-Mansour</name></author><author><name sortKey="Nelson, Bp" uniqKey="Nelson B">BP Nelson</name></author><author><name sortKey="Evens, Am" uniqKey="Evens A">AM Evens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Orem, J" uniqKey="Orem J">J Orem</name></author><author><name sortKey="Mbidde, Ek" uniqKey="Mbidde E">EK Mbidde</name></author><author><name sortKey="Lambert, B" uniqKey="Lambert B">B Lambert</name></author><author><name sortKey="De Sanjose, S" uniqKey="De Sanjose S">S de Sanjose</name></author><author><name sortKey="Weiderpass, E" uniqKey="Weiderpass E">E Weiderpass</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stanfield, Ba" uniqKey="Stanfield B">BA Stanfield</name></author><author><name sortKey="Luftig, Ma" uniqKey="Luftig M">MA Luftig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koganti, S" uniqKey="Koganti S">S Koganti</name></author><author><name sortKey="De La Paz, A" uniqKey="De La Paz A">A de la Paz</name></author><author><name sortKey="Freeman, Af" uniqKey="Freeman A">AF Freeman</name></author><author><name sortKey="Bhaduri Mcintosh, S" uniqKey="Bhaduri Mcintosh S">S Bhaduri-McIntosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koganti, S" uniqKey="Koganti S">S Koganti</name></author><author><name sortKey="Hui Yuen, J" uniqKey="Hui Yuen J">J Hui-Yuen</name></author><author><name sortKey="Mcallister, S" uniqKey="Mcallister S">S McAllister</name></author><author><name sortKey="Gardner, B" uniqKey="Gardner B">B Gardner</name></author><author><name sortKey="Grasser, F" uniqKey="Grasser F">F Grasser</name></author><author><name sortKey="Palendira, U" uniqKey="Palendira U">U Palendira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, J" uniqKey="Smith J">J Smith</name></author><author><name sortKey="Tho, Lm" uniqKey="Tho L">LM Tho</name></author><author><name sortKey="Xu, N" uniqKey="Xu N">N Xu</name></author><author><name sortKey="Gillespie, Da" uniqKey="Gillespie D">DA Gillespie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bartkova, J" uniqKey="Bartkova J">J Bartkova</name></author><author><name sortKey="Horejsi, Z" uniqKey="Horejsi Z">Z Horejsi</name></author><author><name sortKey="Koed, K" uniqKey="Koed K">K Koed</name></author><author><name sortKey="Kramer, A" uniqKey="Kramer A">A Kramer</name></author><author><name sortKey="Tort, F" uniqKey="Tort F">F Tort</name></author><author><name sortKey="Zieger, K" uniqKey="Zieger K">K Zieger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bartkova, J" uniqKey="Bartkova J">J Bartkova</name></author><author><name sortKey="Rezaei, N" uniqKey="Rezaei N">N Rezaei</name></author><author><name sortKey="Liontos, M" uniqKey="Liontos M">M Liontos</name></author><author><name sortKey="Karakaidos, P" uniqKey="Karakaidos P">P Karakaidos</name></author><author><name sortKey="Kletsas, D" uniqKey="Kletsas D">D Kletsas</name></author><author><name sortKey="Issaeva, N" uniqKey="Issaeva N">N Issaeva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Halazonetis, Td" uniqKey="Halazonetis T">TD Halazonetis</name></author><author><name sortKey="Gorgoulis, Vg" uniqKey="Gorgoulis V">VG Gorgoulis</name></author><author><name sortKey="Bartek, J" uniqKey="Bartek J">J Bartek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hafez, Ay" uniqKey="Hafez A">AY Hafez</name></author><author><name sortKey="Messinger, Je" uniqKey="Messinger J">JE Messinger</name></author><author><name sortKey="Mcfadden, K" uniqKey="Mcfadden K">K McFadden</name></author><author><name sortKey="Fenyofalvi, G" uniqKey="Fenyofalvi G">G Fenyofalvi</name></author><author><name sortKey="Shepard, Cn" uniqKey="Shepard C">CN Shepard</name></author><author><name sortKey="Lenzi, Gm" uniqKey="Lenzi G">GM Lenzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mordasini, V" uniqKey="Mordasini V">V Mordasini</name></author><author><name sortKey="Ueda, S" uniqKey="Ueda S">S Ueda</name></author><author><name sortKey="Aslandogmus, R" uniqKey="Aslandogmus R">R Aslandogmus</name></author><author><name sortKey="Berger, C" uniqKey="Berger C">C Berger</name></author><author><name sortKey="Gysin, C" uniqKey="Gysin C">C Gysin</name></author><author><name sortKey="Huhn, D" uniqKey="Huhn D">D Huhn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sirbu, Bm" uniqKey="Sirbu B">BM Sirbu</name></author><author><name sortKey="Mcdonald, Wh" uniqKey="Mcdonald W">WH McDonald</name></author><author><name sortKey="Dungrawala, H" uniqKey="Dungrawala H">H Dungrawala</name></author><author><name sortKey="Badu Nkansah, A" uniqKey="Badu Nkansah A">A Badu-Nkansah</name></author><author><name sortKey="Kavanaugh, Gm" uniqKey="Kavanaugh G">GM Kavanaugh</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dungrawala, H" uniqKey="Dungrawala H">H Dungrawala</name></author><author><name sortKey="Cortez, D" uniqKey="Cortez D">D Cortez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yarbro, Jw" uniqKey="Yarbro J">JW Yarbro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Charache, S" uniqKey="Charache S">S. Charache</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anantha, Rw" uniqKey="Anantha R">RW Anantha</name></author><author><name sortKey="Vassin, Vm" uniqKey="Vassin V">VM Vassin</name></author><author><name sortKey="Borowiec, Ja" uniqKey="Borowiec J">JA Borowiec</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sirbu, Bm" uniqKey="Sirbu B">BM Sirbu</name></author><author><name sortKey="Couch, Fb" uniqKey="Couch F">FB Couch</name></author><author><name sortKey="Feigerle, Jt" uniqKey="Feigerle J">JT Feigerle</name></author><author><name sortKey="Bhaskara, S" uniqKey="Bhaskara S">S Bhaskara</name></author><author><name sortKey="Hiebert, Sw" uniqKey="Hiebert S">SW Hiebert</name></author><author><name sortKey="Cortez, D" uniqKey="Cortez D">D Cortez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morio, T" uniqKey="Morio T">T Morio</name></author><author><name sortKey="Kim, H" uniqKey="Kim H">H Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Burton, Em" uniqKey="Burton E">EM Burton</name></author><author><name sortKey="Bhaduri Mcintosh, S" uniqKey="Bhaduri Mcintosh S">S Bhaduri-McIntosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="White, D" uniqKey="White D">D White</name></author><author><name sortKey="Rafalska Metcalf, Iu" uniqKey="Rafalska Metcalf I">IU Rafalska-Metcalf</name></author><author><name sortKey="Ivanov, Av" uniqKey="Ivanov A">AV Ivanov</name></author><author><name sortKey="Corsinotti, A" uniqKey="Corsinotti A">A Corsinotti</name></author><author><name sortKey="Peng, H" uniqKey="Peng H">H Peng</name></author><author><name sortKey="Lee, Sc" uniqKey="Lee S">SC Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elgueta, R" uniqKey="Elgueta R">R Elgueta</name></author><author><name sortKey="Benson, Mj" uniqKey="Benson M">MJ Benson</name></author><author><name sortKey="De Vries, Vc" uniqKey="De Vries V">VC de Vries</name></author><author><name sortKey="Wasiuk, A" uniqKey="Wasiuk A">A Wasiuk</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y Guo</name></author><author><name sortKey="Noelle, Rj" uniqKey="Noelle R">RJ Noelle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Lw" uniqKey="Wang L">LW Wang</name></author><author><name sortKey="Shen, H" uniqKey="Shen H">H Shen</name></author><author><name sortKey="Nobre, L" uniqKey="Nobre L">L Nobre</name></author><author><name sortKey="Ersing, I" uniqKey="Ersing I">I Ersing</name></author><author><name sortKey="Paulo, Ja" uniqKey="Paulo J">JA Paulo</name></author><author><name sortKey="Trudeau, S" uniqKey="Trudeau S">S Trudeau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lopez Contreras, Aj" uniqKey="Lopez Contreras A">AJ Lopez-Contreras</name></author><author><name sortKey="Ruppen, I" uniqKey="Ruppen I">I Ruppen</name></author><author><name sortKey="Nieto Soler, M" uniqKey="Nieto Soler M">M Nieto-Soler</name></author><author><name sortKey="Murga, M" uniqKey="Murga M">M Murga</name></author><author><name sortKey="Rodriguez Acebes, S" uniqKey="Rodriguez Acebes S">S Rodriguez-Acebes</name></author><author><name sortKey="Remeseiro, S" uniqKey="Remeseiro S">S Remeseiro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dembowski, Ja" uniqKey="Dembowski J">JA Dembowski</name></author><author><name sortKey="Deluca, Na" uniqKey="Deluca N">NA DeLuca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kliszczak, Ae" uniqKey="Kliszczak A">AE Kliszczak</name></author><author><name sortKey="Rainey, Md" uniqKey="Rainey M">MD Rainey</name></author><author><name sortKey="Harhen, B" uniqKey="Harhen B">B Harhen</name></author><author><name sortKey="Boisvert, Fm" uniqKey="Boisvert F">FM Boisvert</name></author><author><name sortKey="Santocanale, C" uniqKey="Santocanale C">C Santocanale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, J" uniqKey="Ma J">J Ma</name></author><author><name sortKey="Mi, C" uniqKey="Mi C">C Mi</name></author><author><name sortKey="Wang, Ks" uniqKey="Wang K">KS Wang</name></author><author><name sortKey="Lee, Jj" uniqKey="Lee J">JJ Lee</name></author><author><name sortKey="Jin, X" uniqKey="Jin X">X Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shahi, P" uniqKey="Shahi P">P Shahi</name></author><author><name sortKey="Wang, Cy" uniqKey="Wang C">CY Wang</name></author><author><name sortKey="Lawson, Da" uniqKey="Lawson D">DA Lawson</name></author><author><name sortKey="Slorach, Em" uniqKey="Slorach E">EM Slorach</name></author><author><name sortKey="Lu, A" uniqKey="Lu A">A Lu</name></author><author><name sortKey="Yu, Y" uniqKey="Yu Y">Y Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Winczura, K" uniqKey="Winczura K">K Winczura</name></author><author><name sortKey="Schmid, M" uniqKey="Schmid M">M Schmid</name></author><author><name sortKey="Iasillo, C" uniqKey="Iasillo C">C Iasillo</name></author><author><name sortKey="Molloy, Kr" uniqKey="Molloy K">KR Molloy</name></author><author><name sortKey="Harder, Lm" uniqKey="Harder L">LM Harder</name></author><author><name sortKey="Andersen, Js" uniqKey="Andersen J">JS Andersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benz, C" uniqKey="Benz C">C Benz</name></author><author><name sortKey="Mulindwa, J" uniqKey="Mulindwa J">J Mulindwa</name></author><author><name sortKey="Ouna, B" uniqKey="Ouna B">B Ouna</name></author><author><name sortKey="Clayton, C" uniqKey="Clayton C">C Clayton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kang, Ms" uniqKey="Kang M">MS Kang</name></author><author><name sortKey="Kieff, E" uniqKey="Kieff E">E Kieff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nikitin, Pa" uniqKey="Nikitin P">PA Nikitin</name></author><author><name sortKey="Yan, Cm" uniqKey="Yan C">CM Yan</name></author><author><name sortKey="Forte, E" uniqKey="Forte E">E Forte</name></author><author><name sortKey="Bocedi, A" uniqKey="Bocedi A">A Bocedi</name></author><author><name sortKey="Tourigny, Jp" uniqKey="Tourigny J">JP Tourigny</name></author><author><name sortKey="White, Re" uniqKey="White R">RE White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cimprich, Ka" uniqKey="Cimprich K">KA Cimprich</name></author><author><name sortKey="Cortez, D" uniqKey="Cortez D">D Cortez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paulsen, Rd" uniqKey="Paulsen R">RD Paulsen</name></author><author><name sortKey="Cimprich, Ka" uniqKey="Cimprich K">KA Cimprich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saldivar, Jc" uniqKey="Saldivar J">JC Saldivar</name></author><author><name sortKey="Cortez, D" uniqKey="Cortez D">D Cortez</name></author><author><name sortKey="Cimprich, Ka" uniqKey="Cimprich K">KA Cimprich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, S" uniqKey="Zhou S">S Zhou</name></author><author><name sortKey="Yan, Y" uniqKey="Yan Y">Y Yan</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Zeng, S" uniqKey="Zeng S">S Zeng</name></author><author><name sortKey="Qian, L" uniqKey="Qian L">L Qian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chakravarthi, B" uniqKey="Chakravarthi B">B Chakravarthi</name></author><author><name sortKey="Rodriguez Pena, Mdc" uniqKey="Rodriguez Pena M">MDC Rodriguez Pena</name></author><author><name sortKey="Agarwal, S" uniqKey="Agarwal S">S Agarwal</name></author><author><name sortKey="Chandrashekar, Ds" uniqKey="Chandrashekar D">DS Chandrashekar</name></author><author><name sortKey="Hodigere Balasubramanya, Sa" uniqKey="Hodigere Balasubramanya S">SA Hodigere Balasubramanya</name></author><author><name sortKey="Jabboure, Fj" uniqKey="Jabboure F">FJ Jabboure</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chakravarthi, B" uniqKey="Chakravarthi B">B Chakravarthi</name></author><author><name sortKey="Goswami, Mt" uniqKey="Goswami M">MT Goswami</name></author><author><name sortKey="Pathi, Ss" uniqKey="Pathi S">SS Pathi</name></author><author><name sortKey="Dodson, M" uniqKey="Dodson M">M Dodson</name></author><author><name sortKey="Chandrashekar, Ds" uniqKey="Chandrashekar D">DS Chandrashekar</name></author><author><name sortKey="Agarwal, S" uniqKey="Agarwal S">S Agarwal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eissmann, M" uniqKey="Eissmann M">M Eissmann</name></author><author><name sortKey="Schwamb, B" uniqKey="Schwamb B">B Schwamb</name></author><author><name sortKey="Melzer, Im" uniqKey="Melzer I">IM Melzer</name></author><author><name sortKey="Moser, J" uniqKey="Moser J">J Moser</name></author><author><name sortKey="Siele, D" uniqKey="Siele D">D Siele</name></author><author><name sortKey="Kohl, U" uniqKey="Kohl U">U Kohl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kwok, Wk" uniqKey="Kwok W">WK Kwok</name></author><author><name sortKey="Ling, Mt" uniqKey="Ling M">MT Ling</name></author><author><name sortKey="Yuen, Hf" uniqKey="Yuen H">HF Yuen</name></author><author><name sortKey="Wong, Yc" uniqKey="Wong Y">YC Wong</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, P" uniqKey="Zhang P">P Zhang</name></author><author><name sortKey="Branson, Oe" uniqKey="Branson O">OE Branson</name></author><author><name sortKey="Freitas, Ma" uniqKey="Freitas M">MA Freitas</name></author><author><name sortKey="Parthun, Mr" uniqKey="Parthun M">MR Parthun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Th Ng, Jp" uniqKey="Th Ng J">JP Th'ng</name></author><author><name sortKey="Sung, R" uniqKey="Sung R">R Sung</name></author><author><name sortKey="Ye, M" uniqKey="Ye M">M Ye</name></author><author><name sortKey="Hendzel, Mj" uniqKey="Hendzel M">MJ Hendzel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name></author><author><name sortKey="Shao, Z" uniqKey="Shao Z">Z Shao</name></author><author><name sortKey="Jiang, W" uniqKey="Jiang W">W Jiang</name></author><author><name sortKey="Lee, Bj" uniqKey="Lee B">BJ Lee</name></author><author><name sortKey="Zha, S" uniqKey="Zha S">S Zha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Verma, S" uniqKey="Verma S">S Verma</name></author><author><name sortKey="De Jesus, P" uniqKey="De Jesus P">P De Jesus</name></author><author><name sortKey="Chanda, Sk" uniqKey="Chanda S">SK Chanda</name></author><author><name sortKey="Verma, Im" uniqKey="Verma I">IM Verma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jurica, Ms" uniqKey="Jurica M">MS Jurica</name></author><author><name sortKey="Licklider, Lj" uniqKey="Licklider L">LJ Licklider</name></author><author><name sortKey="Gygi, Sr" uniqKey="Gygi S">SR Gygi</name></author><author><name sortKey="Grigorieff, N" uniqKey="Grigorieff N">N Grigorieff</name></author><author><name sortKey="Moore, Mj" uniqKey="Moore M">MJ Moore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author><author><name sortKey="Yan, C" uniqKey="Yan C">C Yan</name></author><author><name sortKey="Hang, J" uniqKey="Hang J">J Hang</name></author><author><name sortKey="Finci, Li" uniqKey="Finci L">LI Finci</name></author><author><name sortKey="Lei, J" uniqKey="Lei J">J Lei</name></author><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertram, K" uniqKey="Bertram K">K Bertram</name></author><author><name sortKey="Agafonov, De" uniqKey="Agafonov D">DE Agafonov</name></author><author><name sortKey="Liu, Wt" uniqKey="Liu W">WT Liu</name></author><author><name sortKey="Dybkov, O" uniqKey="Dybkov O">O Dybkov</name></author><author><name sortKey="Will, Cl" uniqKey="Will C">CL Will</name></author><author><name sortKey="Hartmuth, K" uniqKey="Hartmuth K">K Hartmuth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bres, V" uniqKey="Bres V">V Bres</name></author><author><name sortKey="Yoshida, T" uniqKey="Yoshida T">T Yoshida</name></author><author><name sortKey="Pickle, L" uniqKey="Pickle L">L Pickle</name></author><author><name sortKey="Jones, Ka" uniqKey="Jones K">KA Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, S" uniqKey="Zhou S">S Zhou</name></author><author><name sortKey="Fujimuro, M" uniqKey="Fujimuro M">M Fujimuro</name></author><author><name sortKey="Hsieh, Jj" uniqKey="Hsieh J">JJ Hsieh</name></author><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Hayward, Sd" uniqKey="Hayward S">SD Hayward</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Unoki, M" uniqKey="Unoki M">M Unoki</name></author><author><name sortKey="Okutsu, J" uniqKey="Okutsu J">J Okutsu</name></author><author><name sortKey="Nakamura, Y" uniqKey="Nakamura Y">Y Nakamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paschke, L" uniqKey="Paschke L">L Paschke</name></author><author><name sortKey="Rucinski, M" uniqKey="Rucinski M">M Rucinski</name></author><author><name sortKey="Ziolkowska, A" uniqKey="Ziolkowska A">A Ziolkowska</name></author><author><name sortKey="Zemleduch, T" uniqKey="Zemleduch T">T Zemleduch</name></author><author><name sortKey="Malendowicz, W" uniqKey="Malendowicz W">W Malendowicz</name></author><author><name sortKey="Kwias, Z" uniqKey="Kwias Z">Z Kwias</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, X" uniqKey="Jin X">X Jin</name></author><author><name sortKey="Jin, Hr" uniqKey="Jin H">HR Jin</name></author><author><name sortKey="Jung, Hs" uniqKey="Jung H">HS Jung</name></author><author><name sortKey="Lee, Sj" uniqKey="Lee S">SJ Lee</name></author><author><name sortKey="Lee, Jh" uniqKey="Lee J">JH Lee</name></author><author><name sortKey="Lee, Jj" uniqKey="Lee J">JJ Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Hr" uniqKey="Jin H">HR Jin</name></author><author><name sortKey="Jin, X" uniqKey="Jin X">X Jin</name></author><author><name sortKey="Lee, Jj" uniqKey="Lee J">JJ Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peng, Y" uniqKey="Peng Y">Y Peng</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X Shen</name></author><author><name sortKey="Jiang, H" uniqKey="Jiang H">H Jiang</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J Wu</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zheng, Y" uniqKey="Zheng Y">Y Zheng</name></author><author><name sortKey="Yang, C" uniqKey="Yang C">C Yang</name></author><author><name sortKey="Tong, S" uniqKey="Tong S">S Tong</name></author><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y Ding</name></author><author><name sortKey="Deng, W" uniqKey="Deng W">W Deng</name></author><author><name sortKey="Song, D" uniqKey="Song D">D Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blixt, Mke" uniqKey="Blixt M">MKE Blixt</name></author><author><name sortKey="Konjusha, D" uniqKey="Konjusha D">D Konjusha</name></author><author><name sortKey="Ring, H" uniqKey="Ring H">H Ring</name></author><author><name sortKey="Hallbook, F" uniqKey="Hallbook F">F Hallbook</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Urban, N" uniqKey="Urban N">N Urban</name></author><author><name sortKey="Martin Ibanez, R" uniqKey="Martin Ibanez R">R Martin-Ibanez</name></author><author><name sortKey="Herranz, C" uniqKey="Herranz C">C Herranz</name></author><author><name sortKey="Esgleas, M" uniqKey="Esgleas M">M Esgleas</name></author><author><name sortKey="Crespo, E" uniqKey="Crespo E">E Crespo</name></author><author><name sortKey="Pardo, M" uniqKey="Pardo M">M Pardo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shahi, P" uniqKey="Shahi P">P Shahi</name></author><author><name sortKey="Slorach, Em" uniqKey="Slorach E">EM Slorach</name></author><author><name sortKey="Wang, Cy" uniqKey="Wang C">CY Wang</name></author><author><name sortKey="Chou, J" uniqKey="Chou J">J Chou</name></author><author><name sortKey="Lu, A" uniqKey="Lu A">A Lu</name></author><author><name sortKey="Ruderisch, A" uniqKey="Ruderisch A">A Ruderisch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G Lu</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Calabretta, S" uniqKey="Calabretta S">S Calabretta</name></author><author><name sortKey="Richard, S" uniqKey="Richard S">S Richard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jarvelin, Ai" uniqKey="Jarvelin A">AI Jarvelin</name></author><author><name sortKey="Noerenberg, M" uniqKey="Noerenberg M">M Noerenberg</name></author><author><name sortKey="Davis, I" uniqKey="Davis I">I Davis</name></author><author><name sortKey="Castello, A" uniqKey="Castello A">A Castello</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, J" uniqKey="Luo J">J Luo</name></author><author><name sortKey="Emanuele, Mj" uniqKey="Emanuele M">MJ Emanuele</name></author><author><name sortKey="Li, D" uniqKey="Li D">D Li</name></author><author><name sortKey="Creighton, Cj" uniqKey="Creighton C">CJ Creighton</name></author><author><name sortKey="Schlabach, Mr" uniqKey="Schlabach M">MR Schlabach</name></author><author><name sortKey="Westbrook, Tf" uniqKey="Westbrook T">TF Westbrook</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gewurz, Be" uniqKey="Gewurz B">BE Gewurz</name></author><author><name sortKey="Towfic, F" uniqKey="Towfic F">F Towfic</name></author><author><name sortKey="Mar, Jc" uniqKey="Mar J">JC Mar</name></author><author><name sortKey="Shinners, Np" uniqKey="Shinners N">NP Shinners</name></author><author><name sortKey="Takasaki, K" uniqKey="Takasaki K">K Takasaki</name></author><author><name sortKey="Zhao, B" uniqKey="Zhao B">B Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ribeyre, C" uniqKey="Ribeyre C">C Ribeyre</name></author><author><name sortKey="Zellweger, R" uniqKey="Zellweger R">R Zellweger</name></author><author><name sortKey="Chauvin, M" uniqKey="Chauvin M">M Chauvin</name></author><author><name sortKey="Bec, N" uniqKey="Bec N">N Bec</name></author><author><name sortKey="Larroque, C" uniqKey="Larroque C">C Larroque</name></author><author><name sortKey="Lopes, M" uniqKey="Lopes M">M Lopes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dabral, P" uniqKey="Dabral P">P Dabral</name></author><author><name sortKey="Uppal, T" uniqKey="Uppal T">T Uppal</name></author><author><name sortKey="Rossetto, Cc" uniqKey="Rossetto C">CC Rossetto</name></author><author><name sortKey="Verma, Sc" uniqKey="Verma S">SC Verma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Macheret, M" uniqKey="Macheret M">M Macheret</name></author><author><name sortKey="Halazonetis, Td" uniqKey="Halazonetis T">TD Halazonetis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui Yuen, J" uniqKey="Hui Yuen J">J Hui-Yuen</name></author><author><name sortKey="Koganti, S" uniqKey="Koganti S">S Koganti</name></author><author><name sortKey="Bhaduri Mcintosh, S" uniqKey="Bhaduri Mcintosh S">S Bhaduri-McIntosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Burton, Em" uniqKey="Burton E">EM Burton</name></author><author><name sortKey="Koganti, S" uniqKey="Koganti S">S Koganti</name></author><author><name sortKey="Zhi, J" uniqKey="Zhi J">J Zhi</name></author><author><name sortKey="Doyle, F" uniqKey="Doyle F">F Doyle</name></author><author><name sortKey="Tenenbaum, Sa" uniqKey="Tenenbaum S">SA Tenenbaum</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31841561</article-id><article-id pub-id-type="pmc">6936862</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.1008228</article-id><article-id pub-id-type="publisher-id">PPATHOGENS-D-19-01881</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Genetics</subject><subj-group><subject>DNA</subject><subj-group><subject>DNA replication</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Nucleic acids</subject><subj-group><subject>DNA</subject><subj-group><subject>DNA replication</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cellular Types</subject><subj-group><subject>Animal Cells</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>Antibody-Producing Cells</subject><subj-group><subject>B Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>Antibody-Producing Cells</subject><subj-group><subject>B Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>Antibody-Producing Cells</subject><subj-group><subject>B Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cellular Types</subject><subj-group><subject>Animal Cells</subject><subj-group><subject>Blood Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>B Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cellular Types</subject><subj-group><subject>Animal Cells</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>B Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>B Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>B Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cell Processes</subject><subj-group><subject>Cell Cycle and Cell Division</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Virology</subject><subj-group><subject>Viral Replication</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject><subj-group><subject>Spectrum Analysis Techniques</subject><subj-group><subject>Spectrophotometry</subject><subj-group><subject>Cytophotometry</subject><subj-group><subject>Flow Cytometry</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>DNA viruses</subject><subj-group><subject>Herpesviruses</subject><subj-group><subject>Epstein-Barr virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Medical microbiology</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Herpesviruses</subject><subj-group><subject>Epstein-Barr virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and health sciences</subject><subj-group><subject>Pathology and laboratory medicine</subject><subj-group><subject>Pathogens</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Herpesviruses</subject><subj-group><subject>Epstein-Barr virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Herpesviruses</subject><subj-group><subject>Epstein-Barr virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cell Processes</subject><subj-group><subject>Cell Cycle and Cell Division</subject><subj-group><subject>Synthesis Phase</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Genetics</subject><subj-group><subject>DNA</subject><subj-group><subject>DNA repair</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Nucleic acids</subject><subj-group><subject>DNA</subject><subj-group><subject>DNA repair</subject></subj-group></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Novel replisome-associated proteins at cellular replication forks in EBV-transformed B lymphocytes</article-title><alt-title alt-title-type="running-head">Cellular replisomes in EBV-transformed B cells</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Huanzhou</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Visualization</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Perez</surname><given-names>Ramon D.</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Validation</role><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-4247-6715</contrib-id><name><surname>Frey</surname><given-names>Tiffany R.</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Burton</surname><given-names>Eric M.</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mannemuddhu</surname><given-names>Sudha</given-names></name><role content-type="http://credit.casrai.org/">Resources</role><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Haley</surname><given-names>John D.</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>McIntosh</surname><given-names>Michael T.</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Visualization</role><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-2946-9497</contrib-id><name><surname>Bhaduri-McIntosh</surname><given-names>Sumita</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Project administration</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Visualization</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff006"><sup>6</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Division of Infectious Disease, Department of Pediatrics, University of Florida, Gainesville, Florida, United States of America</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New Yordk, Unites States of America</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Division of Nephrology, Dept. of Pediatrics, University of Florida, Gainesville, Florida, United States of America</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Department of Pathology and Stony Brook Proteomics Center, Stony Brook University, Stony Brook, New York, United States of America</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Child Health Research Institute, Department of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Division of Infectious Disease, Departments of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Gewurz</surname><given-names>Benjamin E.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Brigham and Women's Hospital, UNITED STATES</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p>The authors have declared that no competing interests exist.</p></fn><corresp id="cor001">* E-mail: <email>sbhadurimcintosh@ufl.edu</email></corresp></author-notes><pub-date pub-type="epub"><day>16</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>12</month><year>2019</year></pub-date><volume>15</volume><issue>12</issue><elocation-id>e1008228</elocation-id><history><date date-type="received"><day>10</day><month>10</month><year>2019</year></date><date date-type="accepted"><day>20</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 Xu et al</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Xu et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="ppat.1008228.pdf"></self-uri><abstract><p>Epstein-Barr virus (EBV) is an oncogenic herpesvirus and WHO class 1 carcinogen that resides in B lymphocytes of nearly all humans. While silent in most, EBV can cause endemic Burkitt lymphoma in children and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. The pathogenesis of such lymphomas is multifactorial but to a large extent depends on EBV’s ability to aggressively drive cellular DNA replication and B cell proliferation despite cell-intrinsic barriers to replication. One such barrier is oncogenic replication stress which hinders the progression of DNA replication forks. To understand how EBV successfully overcomes replication stress, we examined cellular replication forks in EBV-transformed B cells using iPOND (isolation of Proteins on Nascent DNA)-mass spectrometry and identified several cellular proteins that had not previously been linked to DNA replication. Of eight candidate replisome-associated proteins that we validated at forks in EBV-transformed cells and Burkitt lymphoma-derived cells, three zinc finger proteins (ZFPs) were upregulated early in B cells newly-infected with EBV in culture as well as expressed at high levels in EBV-infected B blasts in the blood of immunocompromised transplant recipients. Expressed highly in S- and G2-phase cells, knockdown of each ZFP resulted in stalling of proliferating cells in the S-phase, cleavage of caspase 3, and cell death. These proteins, newly-identified at replication forks of EBV-transformed and Burkitt lymphoma cells therefore contribute to cell survival and cell cycle progression, and represent novel targets for intervention of EBV-lymphomas while simultaneously offering a window into how the replication machinery may be similarly modified in other cancers.</p></abstract><abstract abstract-type="summary"><title>Author summary</title><p>Cancer cells must overcome chronic replication stress, a central barrier to DNA replication. This is true also for cancers caused by Epstein-Barr virus (EBV). To understand how EBV overcomes this barrier to successfully drive cell proliferation, we isolated proteins associated with the cellular replication machinery in EBV-transformed B lymphocytes and identified several cellular proteins that had not previously been linked to DNA replication in cancer or healthy cells. Three of these were zinc finger proteins enriched at the replication machinery in EBV-transformed and EBV-positive Burkitt lymphoma-derived cells, upregulated in newly-infected B cells, and expressed at high levels in infected B cells from transplant recipients. These zinc finger proteins also contributed towards cell proliferation, survival, and cell cycle progression. While these proteins may also contribute to DNA replication in other cancers, they simultaneously represent potential targets in EBV-cancers, some of which are difficult to treat.</p></abstract><funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id><institution>National Institutes of Health</institution></institution-wrap></funding-source><award-id>AI113134</award-id><principal-award-recipient><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-2946-9497</contrib-id><name><surname>Bhaduri-McIntosh</surname><given-names>Sumita</given-names></name></principal-award-recipient></award-group><funding-statement>M.T.M. was supported by the University of Florida and S.B.-M. was supported by NIH grant R01 AI113134, the Children’s Miracle Network, and the University of Florida. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="6"></fig-count><table-count count="2"></table-count><page-count count="19"></page-count></counts><custom-meta-group><custom-meta><meta-name>PLOS Publication Stage</meta-name><meta-value>vor-update-to-uncorrected-proof</meta-value></custom-meta><custom-meta><meta-name>Publication Update</meta-name><meta-value>2019-12-30</meta-value></custom-meta><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the manuscript and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the manuscript and its Supporting Information files.</p></notes></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Floride</li><li>État de New York</li></region></list><tree><noCountry><name sortKey="Perez, Ramon D" sort="Perez, Ramon D" uniqKey="Perez R" first="Ramon D." last="Perez">Ramon D. Perez</name></noCountry><country name="États-Unis"><region name="Floride"><name sortKey="Xu, Huanzhou" sort="Xu, Huanzhou" uniqKey="Xu H" first="Huanzhou" last="Xu">Huanzhou Xu</name></region><name sortKey="Bhaduri Mcintosh, Sumita" sort="Bhaduri Mcintosh, Sumita" uniqKey="Bhaduri Mcintosh S" first="Sumita" last="Bhaduri-Mcintosh">Sumita Bhaduri-Mcintosh</name><name sortKey="Burton, Eric M" sort="Burton, Eric M" uniqKey="Burton E" first="Eric M." last="Burton">Eric M. Burton</name><name sortKey="Frey, Tiffany R" sort="Frey, Tiffany R" uniqKey="Frey T" first="Tiffany R." last="Frey">Tiffany R. Frey</name><name sortKey="Haley, John D" sort="Haley, John D" uniqKey="Haley J" first="John D." last="Haley">John D. Haley</name><name sortKey="Mannemuddhu, Sudha" sort="Mannemuddhu, Sudha" uniqKey="Mannemuddhu S" first="Sudha" last="Mannemuddhu">Sudha Mannemuddhu</name><name sortKey="Mcintosh, Michael T" sort="Mcintosh, Michael T" uniqKey="Mcintosh M" first="Michael T." last="Mcintosh">Michael T. Mcintosh</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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