The ADP-ribose hydrolase NUDT5 is important for DNA repair
Author
Qi, Hongyun
Wright, Roni
Beato, Miguel
Price, Brendan D.
Publication date
2022-12ISSN
2639-1856
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
57 - Biological sciences in general
Keywords
NUDT5
NUDIX hidrolasa
Reparació de l'ADN
Metabolisme energètic
ATP
PARPs
Mono (ADP-ribosa)
Recombinació homòloga
Cromatina
NUDT5
NUDIX hidrolasa
Reparación de ADN
Metabolismo energético
ATP
PARP
Mono(ADP-ribosa)
Recombinación homóloga
Cromatina
NUDT5
NUDIX hydrolase
DNA repair
Energy metabolism
ATP
PARPs
Mono(ADP-ribose)
Homologous recombination
Chromatin
Pages
13
Publisher
Springer Nature
Collection
41; 12
Is part of
Cell Reports
Citation
Qi, Hongyun; Wright, Roni; Beato, Miguel [et al.]. The ADP-ribose hydrolase NUDT5 is important for DNA repair. Cell Reports, 2022, 41(12), 111866. Disponible en: <https://www.sciencedirect.com/science/article/pii/S2211124722017624?via%3Dihub>. Fecha de acceso: 1 mar. 2023. DOI: 10.1016/j.celrep.2022.111866
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Under a Creative Commons license.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/