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Dispensability of HPF1 for cellular removal of DNA single-strand breaks
K. Hrychova, K. Burdova, Z. Polackova, D. Giamaki, B. Valtorta, J. Brazina, K. Krejcikova, B. Kuttichova, KW. Caldecott, H. Hanzlikova
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
22-00885S
Czech Science Foundation
186122
Charles University
L200522301
Czech Academy of Sciences
RVO - 68378050
institutional funding
LM2023050
MEYS
68378050-KAV-NPUI
RVO
CEP - Centrální evidence projektů
MR/W024128/1
Medical Research Council - United Kingdom
NLK
Directory of Open Access Journals
od 2005
Free Medical Journals
od 1996
PubMed Central
od 1974
Europe PubMed Central
od 1974
Open Access Digital Library
od 1996-01-01 do 2030-12-31
Open Access Digital Library
od 1974-01-01
Open Access Digital Library
od 1996-01-01
Open Access Digital Library
od 1996-01-01
Medline Complete (EBSCOhost)
od 1996-01-01
Oxford Journals Open Access Collection
od 1996-01-01
ROAD: Directory of Open Access Scholarly Resources
od 1974
PubMed
39162207
DOI
10.1093/nar/gkae708
Knihovny.cz E-zdroje
- MeSH
- buněčné linie MeSH
- chromatin metabolismus MeSH
- DNA vazebné proteiny metabolismus genetika MeSH
- histony metabolismus MeSH
- jaderné proteiny metabolismus genetika MeSH
- jednořetězcové zlomy DNA * MeSH
- lidé MeSH
- oprava DNA * MeSH
- poly-ADP-ribosylace MeSH
- poly(ADP-ribosa)polymerasa 1 * metabolismus genetika MeSH
- poly(ADP-ribosa)polymerasy metabolismus genetika MeSH
- protein XRCC1 metabolismus genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In response to DNA damage, the histone PARylation factor 1 (HPF1) regulates PARP1/2 activity, facilitating serine ADP-ribosylation of chromatin-associated factors. While PARP1/2 are known for their role in DNA single-strand break repair (SSBR), the significance of HPF1 in this process remains unclear. Here, we investigated the impact of HPF1 deficiency on cellular survival and SSBR following exposure to various genotoxins. We found that HPF1 loss did not generally increase cellular sensitivity to agents that typically induce DNA single-strand breaks (SSBs) repaired by PARP1. SSBR kinetics in HPF1-deficient cells were largely unaffected, though its absence partially influenced the accumulation of SSB intermediates after exposure to specific genotoxins in certain cell lines, likely due to altered ADP-ribosylation of chromatin. Despite reduced serine mono-ADP-ribosylation, HPF1-deficient cells maintained robust poly-ADP-ribosylation at SSB sites, possibly reflecting PARP1 auto-poly-ADP-ribosylation at non-serine residues. Notably, poly-ADP-ribose chains were sufficient to recruit the DNA repair factor XRCC1, which may explain the relatively normal SSBR capacity in HPF1-deficient cells. These findings suggest that HPF1 and histone serine ADP-ribosylation are largely dispensable for PARP1-dependent SSBR in response to genotoxic stress, highlighting the complexity of mechanisms that maintain genomic stability and chromatin remodeling.
Faculty of Science Charles University Prague Prague 2128 43 Czech Republic
Genome Damage and Stability Centre University of Sussex Falmer Brighton BN1 9RQ UK
Institute of Animal Pathology Vetsuisse Faculty University of Bern Bern 3012 Switzerland
Citace poskytuje Crossref.org
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