The ADP-ribose hydrolase NUDT5 is important for DNA repair
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- dc.contributor.author Qi, Hongyun
- dc.contributor.author Wright, Roni H.G.
- dc.contributor.author Beato, Miguel
- dc.contributor.author Price, Brendan D.
- dc.date.accessioned 2023-02-23T07:03:39Z
- dc.date.available 2023-02-23T07:03:39Z
- dc.date.issued 2022
- dc.description.abstract 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Qi H, Grace Wright RH, Beato M, Price BD. The ADP-ribose hydrolase NUDT5 is important for DNA repair. Cell Rep. 2022 Dec 20;41(12):111866. DOI: 10.1016/j.celrep.2022.111866
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2022.111866
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/55868
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell Rep. 2022 Dec 20;41(12):111866
- dc.rights © 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword ATP
- dc.subject.keyword CP: Cell biology
- dc.subject.keyword CP: Molecular biology
- dc.subject.keyword DNA repair
- dc.subject.keyword NUDIX hydrolase
- dc.subject.keyword NUDT5
- dc.subject.keyword PARPs
- dc.subject.keyword Chromatin
- dc.subject.keyword Energy metabolism
- dc.subject.keyword Homologous recombination
- dc.subject.keyword Mono(ADP-ribose)
- dc.title The ADP-ribose hydrolase NUDT5 is important for DNA repair
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion