RAD6 Promotes Homologous Recombination Repair by Activating the Autophagy-Mediated Degradation of Heterochromatin Protein HP1
Identifieur interne : 001826 ( Main/Exploration ); précédent : 001825; suivant : 001827RAD6 Promotes Homologous Recombination Repair by Activating the Autophagy-Mediated Degradation of Heterochromatin Protein HP1
Auteurs : Su Chen [République populaire de Chine] ; Chen Wang [République populaire de Chine] ; Luxi Sun [États-Unis, République populaire de Chine] ; Da-Liang Wang [République populaire de Chine] ; Lu Chen [République populaire de Chine] ; Zhuan Huang [République populaire de Chine] ; Qi Yang [République populaire de Chine] ; Jie Gao [République populaire de Chine] ; Xi-Bin Yang [République populaire de Chine] ; Jian-Feng Chang [République populaire de Chine] ; Ping Chen [République populaire de Chine] ; Li Lan [États-Unis] ; Zhiyong Mao [République populaire de Chine] ; Fang-Lin Sun [République populaire de Chine]Source :
- Molecular and Cellular Biology [ 0270-7306 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Autophagie, Réparation de l'ADN par recombinaison.
- métabolisme : Hétérochromatine, Protéines chromosomiques nonhistones, Ubiquitin-conjugating enzymes.
- Humains, Lignée cellulaire.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Chromosomal Proteins, Non-Histone, Heterochromatin, Ubiquitin-Conjugating Enzymes.
- genetics : Autophagy, Recombinational DNA Repair.
- Cell Line, Humans.
Abstract
Efficient DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. Unrepaired or misrepaired DSBs cause chromosomal rearrangements that can result in severe consequences, such as tumorigenesis. RAD6 is an E2 ubiquitin-conjugating enzyme that plays a pivotal role in repairing UV-induced DNA damage. Here, we present evidence that RAD6 is also required for DNA DSB repair via homologous recombination (HR) by specifically regulating the degradation of heterochromatin protein 1α (HP1α). Our study indicates that RAD6 physically interacts with HP1α and ubiquitinates HP1α at residue K154, thereby promoting HP1α degradation through the autophagy pathway and eventually leading to an open chromatin structure that facilitates efficient HR DSB repair. Furthermore, bioinformatics studies have indicated that the expression of RAD6 and HP1α exhibits an inverse relationship and correlates with the survival rate of patients.
Url:
DOI: 10.1128/MCB.01044-14
PubMed: 25384975
PubMed Central: 4272427
Affiliations:
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Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">UNEP-Tongji Institute of Environment for Sustainable Development, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>UNEP-Tongji Institute of Environment for Sustainable Development, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Luxi" sort="Sun, Luxi" uniqKey="Sun L" first="Luxi" last="Sun">Luxi Sun</name><affiliation wicri:level="2"><nlm:aff id="aff3">University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff4">School of Medicine, Tsinghua University, Beijing, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Medicine, Tsinghua University, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Da Liang" sort="Wang, Da Liang" uniqKey="Wang D" first="Da-Liang" last="Wang">Da-Liang Wang</name><affiliation wicri:level="3"><nlm:aff id="aff4">School of Medicine, Tsinghua University, Beijing, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Medicine, Tsinghua University, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Zhuan" sort="Huang, Zhuan" uniqKey="Huang Z" first="Zhuan" last="Huang">Zhuan Huang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Qi" sort="Yang, Qi" uniqKey="Yang Q" first="Qi" last="Yang">Qi Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gao, Jie" sort="Gao, Jie" uniqKey="Gao J" first="Jie" last="Gao">Jie Gao</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Xi Bin" sort="Yang, Xi Bin" uniqKey="Yang X" first="Xi-Bin" last="Yang">Xi-Bin Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Jian Feng" sort="Chang, Jian Feng" uniqKey="Chang J" first="Jian-Feng" last="Chang">Jian-Feng Chang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Ping" sort="Chen, Ping" uniqKey="Chen P" first="Ping" last="Chen">Ping Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Lan, Li" sort="Lan, Li" uniqKey="Lan L" first="Li" last="Lan">Li Lan</name><affiliation wicri:level="2"><nlm:aff id="aff3">University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Mao, Zhiyong" sort="Mao, Zhiyong" uniqKey="Mao Z" first="Zhiyong" last="Mao">Zhiyong Mao</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Fang Lin" sort="Sun, Fang Lin" uniqKey="Sun F" first="Fang-Lin" last="Sun">Fang-Lin Sun</name><affiliation wicri:level="1"><nlm:aff id="aff1">Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular and Cellular Biology</title><idno type="ISSN">0270-7306</idno><idno type="eISSN">1098-5549</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Autophagy (genetics)</term><term>Cell Line</term><term>Chromosomal Proteins, Non-Histone (metabolism)</term><term>Heterochromatin (metabolism)</term><term>Humans</term><term>Recombinational DNA Repair (genetics)</term><term>Ubiquitin-Conjugating Enzymes (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Autophagie (génétique)</term><term>Humains</term><term>Hétérochromatine (métabolisme)</term><term>Lignée cellulaire</term><term>Protéines chromosomiques nonhistones (métabolisme)</term><term>Réparation de l'ADN par recombinaison (génétique)</term><term>Ubiquitin-conjugating enzymes (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Chromosomal Proteins, Non-Histone</term><term>Heterochromatin</term><term>Ubiquitin-Conjugating Enzymes</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Autophagy</term><term>Recombinational DNA Repair</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Autophagie</term><term>Réparation de l'ADN par recombinaison</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Hétérochromatine</term><term>Protéines chromosomiques nonhistones</term><term>Ubiquitin-conjugating enzymes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Lignée cellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Efficient DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. Unrepaired or misrepaired DSBs cause chromosomal rearrangements that can result in severe consequences, such as tumorigenesis. RAD6 is an E2 ubiquitin-conjugating enzyme that plays a pivotal role in repairing UV-induced DNA damage. Here, we present evidence that RAD6 is also required for DNA DSB repair via homologous recombination (HR) by specifically regulating the degradation of heterochromatin protein 1α (HP1α). Our study indicates that RAD6 physically interacts with HP1α and ubiquitinates HP1α at residue K154, thereby promoting HP1α degradation through the autophagy pathway and eventually leading to an open chromatin structure that facilitates efficient HR DSB repair. Furthermore, bioinformatics studies have indicated that the expression of RAD6 and HP1α exhibits an inverse relationship and correlates with the survival rate of patients.</p></div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Pennsylvanie</li></region><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Chen, Su" sort="Chen, Su" uniqKey="Chen S" first="Su" last="Chen">Su Chen</name></noRegion><name sortKey="Chang, Jian Feng" sort="Chang, Jian Feng" uniqKey="Chang J" first="Jian-Feng" last="Chang">Jian-Feng Chang</name><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name><name sortKey="Chen, Ping" sort="Chen, Ping" uniqKey="Chen P" first="Ping" last="Chen">Ping Chen</name><name sortKey="Gao, Jie" sort="Gao, Jie" uniqKey="Gao J" first="Jie" last="Gao">Jie Gao</name><name sortKey="Huang, Zhuan" sort="Huang, Zhuan" uniqKey="Huang Z" first="Zhuan" last="Huang">Zhuan Huang</name><name sortKey="Mao, Zhiyong" sort="Mao, Zhiyong" uniqKey="Mao Z" first="Zhiyong" last="Mao">Zhiyong Mao</name><name sortKey="Sun, Fang Lin" sort="Sun, Fang Lin" uniqKey="Sun F" first="Fang-Lin" last="Sun">Fang-Lin Sun</name><name sortKey="Sun, Luxi" sort="Sun, Luxi" uniqKey="Sun L" first="Luxi" last="Sun">Luxi Sun</name><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name><name sortKey="Wang, Da Liang" sort="Wang, Da Liang" uniqKey="Wang D" first="Da-Liang" last="Wang">Da-Liang Wang</name><name sortKey="Yang, Qi" sort="Yang, Qi" uniqKey="Yang Q" first="Qi" last="Yang">Qi Yang</name><name sortKey="Yang, Xi Bin" sort="Yang, Xi Bin" uniqKey="Yang X" first="Xi-Bin" last="Yang">Xi-Bin Yang</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Sun, Luxi" sort="Sun, Luxi" uniqKey="Sun L" first="Luxi" last="Sun">Luxi Sun</name></region><name sortKey="Lan, Li" sort="Lan, Li" uniqKey="Lan L" first="Li" last="Lan">Li Lan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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