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Dispensability of HPF1 for cellular removal of DNA single-strand breaks

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00604432" target="_blank" >RIV/68378050:_____/24:00604432 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11310/24:10484274

  • Result on the web

    <a href="https://academic.oup.com/nar/article/52/18/10986/7736811" target="_blank" >https://academic.oup.com/nar/article/52/18/10986/7736811</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1093/nar/gkae708" target="_blank" >10.1093/nar/gkae708</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Dispensability of HPF1 for cellular removal of DNA single-strand breaks

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Nucleic Acids Research

  • ISSN

    0305-1048

  • e-ISSN

    1362-4962

  • Volume of the periodical

    52

  • Issue of the periodical within the volume

    18

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    13

  • Pages from-to

    10986-10998

  • UT code for WoS article

    001293718200001

  • EID of the result in the Scopus database

    2-s2.0-85206278076