Hrychova, Kristyna; Burdova, Kamila; Polackova, Zuzana; Giamaki, Despoina; Valtorta, Beatrice; Brazina, Jan; Krejcikova, Katerina; Kuttichova, Barbora; Caldecott, Keith W; Hanzlikova, Hana (2024). Dispensability of HPF1 for cellular removal of DNA single-strand breaks. (In Press). Nucleic acids research Oxford University Press 10.1093/nar/gkae708
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology 05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) |
UniBE Contributor: |
Giamaki, Despoina |
ISSN: |
0305-1048 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
21 Aug 2024 09:49 |
Last Modified: |
22 Aug 2024 07:10 |
Publisher DOI: |
10.1093/nar/gkae708 |
PubMed ID: |
39162207 |
BORIS DOI: |
10.48350/199870 |
URI: |
https://boris.unibe.ch/id/eprint/199870 |
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