Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli.
Identifieur interne : 000404 ( Main/Exploration ); précédent : 000403; suivant : 000405Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli.
Auteurs : Ashwani Kumar [Canada] ; Natalia Beloglazova [Canada] ; Cedoljub Bundalovic-Torma [Canada] ; Sadhna Phanse [Canada] ; Viktor Deineko [Canada] ; Alla Gagarinova [Canada] ; Gabriel Musso [États-Unis] ; James Vlasblom [Canada] ; Sofia Lemak [Canada] ; Mohsen Hooshyar [Canada] ; Zoran Minic [Canada] ; Omar Wagih [Canada] ; Roberto Mosca [Espagne] ; Patrick Aloy [Espagne] ; Ashkan Golshani [Canada] ; John Parkinson [Canada] ; Andrew Emili [Canada] ; Alexander F. Yakunin [Canada] ; Mohan Babu [Canada]Source :
- Cell reports [ 2211-1247 ] ; 2016.
English descriptors
- KwdEn :
- Catalytic Domain, DNA (metabolism), DNA Repair, Deoxyribonucleases (chemistry), Deoxyribonucleases (genetics), Deoxyribonucleases (metabolism), Endodeoxyribonucleases (chemistry), Endodeoxyribonucleases (genetics), Endodeoxyribonucleases (metabolism), Epistasis, Genetic, Escherichia coli (genetics), Escherichia coli (metabolism), Escherichia coli Proteins (chemistry), Escherichia coli Proteins (genetics), Escherichia coli Proteins (metabolism), Gene Regulatory Networks, Mutagenesis, RNA (metabolism).
- MESH :
- chemical , chemistry : Deoxyribonucleases, Endodeoxyribonucleases, Escherichia coli Proteins.
- chemical , genetics : Deoxyribonucleases, Endodeoxyribonucleases, Escherichia coli Proteins.
- chemical , metabolism : DNA, Deoxyribonucleases, Endodeoxyribonucleases, Escherichia coli Proteins, RNA.
- genetics : Escherichia coli.
- metabolism : Escherichia coli.
- Catalytic Domain, DNA Repair, Epistasis, Genetic, Gene Regulatory Networks, Mutagenesis.
Abstract
As antibiotic resistance is increasingly becoming a public health concern, an improved understanding of the bacterial DNA damage response (DDR), which is commonly targeted by antibiotics, could be of tremendous therapeutic value. Although the genetic components of the bacterial DDR have been studied extensively in isolation, how the underlying biological pathways interact functionally remains unclear. Here, we address this by performing systematic, unbiased, quantitative synthetic genetic interaction (GI) screens and uncover widespread changes in the GI network of the entire genomic integrity apparatus of Escherichia coli under standard and DNA-damaging growth conditions. The GI patterns of untreated cultures implicated two previously uncharacterized proteins (YhbQ and YqgF) as nucleases, whereas reorganization of the GI network after DNA damage revealed DDR roles for both annotated and uncharacterized genes. Analyses of pan-bacterial conservation patterns suggest that DDR mechanisms and functional relationships are near universal, highlighting a modular and highly adaptive genomic stress response.
DOI: 10.1016/j.celrep.2015.12.060
PubMed: 26774489
Affiliations:
- Canada, Espagne, États-Unis
- Manitoba, Massachusetts, Ontario
- Saskatchewan, Toronto
- Université de Regina, Université de Toronto
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Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Musso, Gabriel" sort="Musso, Gabriel" uniqKey="Musso G" first="Gabriel" last="Musso">Gabriel Musso</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women's Hospital, Boston, 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Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Hooshyar, Mohsen" sort="Hooshyar, Mohsen" uniqKey="Hooshyar M" first="Mohsen" last="Hooshyar">Mohsen Hooshyar</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Carleton University, Ottawa, ON K1S 5B6</wicri:regionArea><wicri:noRegion>ON K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Minic, Zoran" sort="Minic, Zoran" uniqKey="Minic Z" first="Zoran" last="Minic">Zoran Minic</name><affiliation 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Lluís Companys 23, Barcelona, 08010, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/Baldiri i Reixac 10-12, Barcelona, 08028, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, Barcelona, 08010, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author><author><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Carleton University, Ottawa, ON K1S 5B6</wicri:regionArea><wicri:noRegion>ON K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><affiliation wicri:level="4"><nlm:affiliation>Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><affiliation wicri:level="4"><nlm:affiliation>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Yakunin, Alexander F" sort="Yakunin, Alexander F" uniqKey="Yakunin A" first="Alexander F" last="Yakunin">Alexander F. Yakunin</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Babu, Mohan" sort="Babu, Mohan" uniqKey="Babu M" first="Mohan" last="Babu">Mohan Babu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada. Electronic address: mohan.babu@uregina.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26774489</idno><idno type="pmid">26774489</idno><idno type="doi">10.1016/j.celrep.2015.12.060</idno><idno type="wicri:Area/PubMed/Corpus">000304</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000304</idno><idno type="wicri:Area/PubMed/Curation">000304</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000304</idno><idno type="wicri:Area/PubMed/Checkpoint">000304</idno><idno type="wicri:explorRef" 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type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Beloglazova, Natalia" sort="Beloglazova, Natalia" uniqKey="Beloglazova N" first="Natalia" last="Beloglazova">Natalia Beloglazova</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Bundalovic Torma, Cedoljub" sort="Bundalovic Torma, Cedoljub" uniqKey="Bundalovic Torma C" first="Cedoljub" last="Bundalovic-Torma">Cedoljub Bundalovic-Torma</name><affiliation wicri:level="4"><nlm:affiliation>Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Phanse, Sadhna" sort="Phanse, Sadhna" uniqKey="Phanse S" first="Sadhna" last="Phanse">Sadhna Phanse</name><affiliation wicri:level="4"><nlm:affiliation>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Regina, Regina, SK S4S 0A2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Deineko, Viktor" sort="Deineko, Viktor" uniqKey="Deineko V" first="Viktor" last="Deineko">Viktor Deineko</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Gagarinova, Alla" sort="Gagarinova, Alla" uniqKey="Gagarinova A" first="Alla" last="Gagarinova">Alla Gagarinova</name><affiliation wicri:level="4"><nlm:affiliation>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Musso, Gabriel" sort="Musso, Gabriel" uniqKey="Musso G" first="Gabriel" last="Musso">Gabriel Musso</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Harvard Medical School and Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Vlasblom, James" sort="Vlasblom, James" uniqKey="Vlasblom J" first="James" last="Vlasblom">James Vlasblom</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Lemak, Sofia" sort="Lemak, Sofia" uniqKey="Lemak S" first="Sofia" last="Lemak">Sofia Lemak</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Hooshyar, Mohsen" sort="Hooshyar, Mohsen" uniqKey="Hooshyar M" first="Mohsen" last="Hooshyar">Mohsen Hooshyar</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Carleton University, Ottawa, ON K1S 5B6</wicri:regionArea><wicri:noRegion>ON K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Minic, Zoran" sort="Minic, Zoran" uniqKey="Minic Z" first="Zoran" last="Minic">Zoran Minic</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Wagih, Omar" sort="Wagih, Omar" uniqKey="Wagih O" first="Omar" last="Wagih">Omar Wagih</name><affiliation wicri:level="4"><nlm:affiliation>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Mosca, Roberto" sort="Mosca, Roberto" uniqKey="Mosca R" first="Roberto" last="Mosca">Roberto Mosca</name><affiliation wicri:level="1"><nlm:affiliation>Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/Baldiri i Reixac 10-12, Barcelona, 08028, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/Baldiri i Reixac 10-12, Barcelona, 08028, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author><author><name sortKey="Aloy, Patrick" sort="Aloy, Patrick" uniqKey="Aloy P" first="Patrick" last="Aloy">Patrick Aloy</name><affiliation wicri:level="1"><nlm:affiliation>Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/Baldiri i Reixac 10-12, Barcelona, 08028, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, Barcelona, 08010, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/Baldiri i Reixac 10-12, Barcelona, 08028, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, Barcelona, 08010, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author><author><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, Carleton University, Ottawa, ON K1S 5B6</wicri:regionArea><wicri:noRegion>ON K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><affiliation wicri:level="4"><nlm:affiliation>Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G OX4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><affiliation wicri:level="4"><nlm:affiliation>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Terrence Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Yakunin, Alexander F" sort="Yakunin, Alexander F" uniqKey="Yakunin A" first="Alexander F" last="Yakunin">Alexander F. Yakunin</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Babu, Mohan" sort="Babu, Mohan" uniqKey="Babu M" first="Mohan" last="Babu">Mohan Babu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada. Electronic address: mohan.babu@uregina.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Regina, Regina, SK S4S 0A2</wicri:regionArea><orgName type="university">Université de Regina</orgName><placeName><settlement type="city">Saskatchewan</settlement><region type="state">Manitoba</region></placeName></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Catalytic Domain</term><term>DNA (metabolism)</term><term>DNA Repair</term><term>Deoxyribonucleases (chemistry)</term><term>Deoxyribonucleases (genetics)</term><term>Deoxyribonucleases (metabolism)</term><term>Endodeoxyribonucleases (chemistry)</term><term>Endodeoxyribonucleases (genetics)</term><term>Endodeoxyribonucleases (metabolism)</term><term>Epistasis, Genetic</term><term>Escherichia coli (genetics)</term><term>Escherichia coli (metabolism)</term><term>Escherichia coli Proteins (chemistry)</term><term>Escherichia coli Proteins (genetics)</term><term>Escherichia coli Proteins (metabolism)</term><term>Gene Regulatory Networks</term><term>Mutagenesis</term><term>RNA (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Deoxyribonucleases</term><term>Endodeoxyribonucleases</term><term>Escherichia coli Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Deoxyribonucleases</term><term>Endodeoxyribonucleases</term><term>Escherichia coli Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA</term><term>Deoxyribonucleases</term><term>Endodeoxyribonucleases</term><term>Escherichia coli Proteins</term><term>RNA</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Escherichia coli</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Catalytic Domain</term><term>DNA Repair</term><term>Epistasis, Genetic</term><term>Gene Regulatory Networks</term><term>Mutagenesis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">As antibiotic resistance is increasingly becoming a public health concern, an improved understanding of the bacterial DNA damage response (DDR), which is commonly targeted by antibiotics, could be of tremendous therapeutic value. Although the genetic components of the bacterial DDR have been studied extensively in isolation, how the underlying biological pathways interact functionally remains unclear. Here, we address this by performing systematic, unbiased, quantitative synthetic genetic interaction (GI) screens and uncover widespread changes in the GI network of the entire genomic integrity apparatus of Escherichia coli under standard and DNA-damaging growth conditions. The GI patterns of untreated cultures implicated two previously uncharacterized proteins (YhbQ and YqgF) as nucleases, whereas reorganization of the GI network after DNA damage revealed DDR roles for both annotated and uncharacterized genes. Analyses of pan-bacterial conservation patterns suggest that DDR mechanisms and functional relationships are near universal, highlighting a modular and highly adaptive genomic stress response.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Espagne</li><li>États-Unis</li></country><region><li>Manitoba</li><li>Massachusetts</li><li>Ontario</li></region><settlement><li>Saskatchewan</li><li>Toronto</li></settlement><orgName><li>Université de Regina</li><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Manitoba"><name sortKey="Kumar, Ashwani" sort="Kumar, Ashwani" uniqKey="Kumar A" first="Ashwani" last="Kumar">Ashwani Kumar</name></region><name sortKey="Babu, Mohan" sort="Babu, Mohan" uniqKey="Babu M" first="Mohan" last="Babu">Mohan Babu</name><name sortKey="Beloglazova, Natalia" sort="Beloglazova, Natalia" uniqKey="Beloglazova N" first="Natalia" last="Beloglazova">Natalia Beloglazova</name><name sortKey="Bundalovic Torma, Cedoljub" sort="Bundalovic Torma, Cedoljub" uniqKey="Bundalovic Torma C" first="Cedoljub" last="Bundalovic-Torma">Cedoljub Bundalovic-Torma</name><name sortKey="Deineko, Viktor" sort="Deineko, Viktor" uniqKey="Deineko V" first="Viktor" last="Deineko">Viktor Deineko</name><name sortKey="Emili, Andrew" sort="Emili, Andrew" uniqKey="Emili A" first="Andrew" last="Emili">Andrew Emili</name><name sortKey="Gagarinova, Alla" sort="Gagarinova, Alla" uniqKey="Gagarinova A" first="Alla" last="Gagarinova">Alla Gagarinova</name><name sortKey="Golshani, Ashkan" sort="Golshani, Ashkan" uniqKey="Golshani A" first="Ashkan" last="Golshani">Ashkan Golshani</name><name sortKey="Hooshyar, Mohsen" sort="Hooshyar, Mohsen" uniqKey="Hooshyar M" first="Mohsen" last="Hooshyar">Mohsen Hooshyar</name><name sortKey="Lemak, Sofia" sort="Lemak, Sofia" uniqKey="Lemak S" first="Sofia" last="Lemak">Sofia Lemak</name><name sortKey="Minic, Zoran" sort="Minic, Zoran" uniqKey="Minic Z" first="Zoran" last="Minic">Zoran Minic</name><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><name sortKey="Phanse, Sadhna" sort="Phanse, Sadhna" uniqKey="Phanse S" first="Sadhna" last="Phanse">Sadhna Phanse</name><name sortKey="Vlasblom, James" sort="Vlasblom, James" uniqKey="Vlasblom J" first="James" last="Vlasblom">James Vlasblom</name><name sortKey="Wagih, Omar" sort="Wagih, Omar" uniqKey="Wagih O" first="Omar" last="Wagih">Omar Wagih</name><name sortKey="Yakunin, Alexander F" sort="Yakunin, Alexander F" uniqKey="Yakunin A" first="Alexander F" last="Yakunin">Alexander F. Yakunin</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Musso, Gabriel" sort="Musso, Gabriel" uniqKey="Musso G" first="Gabriel" last="Musso">Gabriel Musso</name></region></country><country name="Espagne"><noRegion><name sortKey="Mosca, Roberto" sort="Mosca, Roberto" uniqKey="Mosca R" first="Roberto" last="Mosca">Roberto Mosca</name></noRegion><name sortKey="Aloy, Patrick" sort="Aloy, Patrick" uniqKey="Aloy P" first="Patrick" last="Aloy">Patrick Aloy</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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