The ADP-ribose hydrolase NUDT5 is important for DNA repair
DNA damage leads to rapid synthesis of poly(ADP-ribose) (pADPr), which is important for damage signaling and repair. pADPr chains are removed by poly(ADP-ribose) glycohydrolase (PARG), releasing free mono(ADP-ribose) (mADPr). Here, we show that the NUDIX hydrolase NUDT5, which can hydrolyze mADPr to...
| Autores: | , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2022 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/55868 |
| Acesso em linha: | http://hdl.handle.net/10230/55868 http://dx.doi.org/10.1016/j.celrep.2022.111866 |
| Access Level: | Acceso aberto |
| Palavra-chave: | ATP CP: Cell biology CP: Molecular biology DNA repair NUDIX hydrolase NUDT5 PARPs Chromatin Energy metabolism Homologous recombination Mono(ADP-ribose) |
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The ADP-ribose hydrolase NUDT5 is important for DNA repairQi, HongyunWright, Roni H.G.Beato, MiguelPrice, Brendan D.ATPCP: Cell biologyCP: Molecular biologyDNA repairNUDIX hydrolaseNUDT5PARPsChromatinEnergy metabolismHomologous recombinationMono(ADP-ribose)DNA damage leads to rapid synthesis of poly(ADP-ribose) (pADPr), which is important for damage signaling and repair. pADPr chains are removed by poly(ADP-ribose) glycohydrolase (PARG), releasing free mono(ADP-ribose) (mADPr). Here, we show that the NUDIX hydrolase NUDT5, which can hydrolyze mADPr to ribose-5-phosphate and either AMP or ATP, is recruited to damage sites through interaction with PARG. NUDT5 does not regulate PARP or PARG activity. Instead, loss of NUDT5 reduces basal cellular ATP levels and exacerbates the decrease in cellular ATP that occurs during DNA repair. Further, loss of NUDT5 activity impairs RAD51 recruitment, attenuates the phosphorylation of key DNA-repair proteins, and reduces both H2A.Z exchange at damage sites and repair by homologous recombination. The ability of NUDT5 to hydrolyze mADPr, and/or regulate cellular ATP, may therefore be important for efficient DNA repair. Targeting NUDT5 to disrupt PAR/mADPr and energy metabolism may be an effective anti-cancer strategy.Elsevier202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/55868http://dx.doi.org/10.1016/j.celrep.2022.111866reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCell Rep. 2022 Dec 20;41(12):111866© 2022 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/558682026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
The ADP-ribose hydrolase NUDT5 is important for DNA repair |
| title |
The ADP-ribose hydrolase NUDT5 is important for DNA repair |
| spellingShingle |
The ADP-ribose hydrolase NUDT5 is important for DNA repair Qi, Hongyun ATP CP: Cell biology CP: Molecular biology DNA repair NUDIX hydrolase NUDT5 PARPs Chromatin Energy metabolism Homologous recombination Mono(ADP-ribose) |
| title_short |
The ADP-ribose hydrolase NUDT5 is important for DNA repair |
| title_full |
The ADP-ribose hydrolase NUDT5 is important for DNA repair |
| title_fullStr |
The ADP-ribose hydrolase NUDT5 is important for DNA repair |
| title_full_unstemmed |
The ADP-ribose hydrolase NUDT5 is important for DNA repair |
| title_sort |
The ADP-ribose hydrolase NUDT5 is important for DNA repair |
| dc.creator.none.fl_str_mv |
Qi, Hongyun Wright, Roni H.G. Beato, Miguel Price, Brendan D. |
| author |
Qi, Hongyun |
| author_facet |
Qi, Hongyun Wright, Roni H.G. Beato, Miguel Price, Brendan D. |
| author_role |
author |
| author2 |
Wright, Roni H.G. Beato, Miguel Price, Brendan D. |
| author2_role |
author author author |
| dc.subject.none.fl_str_mv |
ATP CP: Cell biology CP: Molecular biology DNA repair NUDIX hydrolase NUDT5 PARPs Chromatin Energy metabolism Homologous recombination Mono(ADP-ribose) |
| topic |
ATP CP: Cell biology CP: Molecular biology DNA repair NUDIX hydrolase NUDT5 PARPs Chromatin Energy metabolism Homologous recombination Mono(ADP-ribose) |
| description |
DNA damage leads to rapid synthesis of poly(ADP-ribose) (pADPr), which is important for damage signaling and repair. pADPr chains are removed by poly(ADP-ribose) glycohydrolase (PARG), releasing free mono(ADP-ribose) (mADPr). Here, we show that the NUDIX hydrolase NUDT5, which can hydrolyze mADPr to ribose-5-phosphate and either AMP or ATP, is recruited to damage sites through interaction with PARG. NUDT5 does not regulate PARP or PARG activity. Instead, loss of NUDT5 reduces basal cellular ATP levels and exacerbates the decrease in cellular ATP that occurs during DNA repair. Further, loss of NUDT5 activity impairs RAD51 recruitment, attenuates the phosphorylation of key DNA-repair proteins, and reduces both H2A.Z exchange at damage sites and repair by homologous recombination. The ability of NUDT5 to hydrolyze mADPr, and/or regulate cellular ATP, may therefore be important for efficient DNA repair. Targeting NUDT5 to disrupt PAR/mADPr and energy metabolism may be an effective anti-cancer strategy. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2023 2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/55868 http://dx.doi.org/10.1016/j.celrep.2022.111866 |
| url |
http://hdl.handle.net/10230/55868 http://dx.doi.org/10.1016/j.celrep.2022.111866 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Cell Rep. 2022 Dec 20;41(12):111866 |
| dc.rights.none.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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