PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F22%3A00128165" target="_blank" >RIV/00216224:14110/22:00128165 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/nar/article/50/21/12291/6882108?login=true" target="_blank" >https://academic.oup.com/nar/article/50/21/12291/6882108?login=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkac1153" target="_blank" >10.1093/nar/gkac1153</a>
Alternative languages
Result language
angličtina
Original language name
PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis
Original language description
Meiotic chromosome segregation relies on programmed DNA double-strand break induction. These are in turn repaired by homologous recombination, generating physical attachments between the parental chromosomes called crossovers. A subset of breaks yields recombinant outcomes, while crossover-independent mechanisms repair the majority of lesions. The balance between different repair pathways is crucial to ensure genome integrity. We show that Caenorhabditis elegans BRC-1/BRCA1-BRD-1/BARD1 and PARG-1/PARG form a complex in vivo, essential for accurate DNA repair in the germline. Simultaneous depletion of BRC-1 and PARG-1 causes synthetic lethality due to reduced crossover formation and impaired break repair, evidenced by hindered RPA-1 removal and presence of aberrant chromatin bodies in diakinesis nuclei, whose formation depends on spo-11 function. These factors undergo a similar yet independent loading in developing oocytes, consistent with operating in different pathways. Abrogation of KU- or Theta-mediated end joining elicits opposite effects in brc-1; parg-1 doubles, suggesting a profound impact in influencing DNA repair pathway choice by BRC-1-PARG-1. Importantly, lack of PARG-1 catalytic activity suppresses untimely accumulation of RAD-51 foci in brc-1 mutants but is only partially required for fertility. Our data show that BRC-1/BRD-1-PARG-1 joint function is essential for genome integrity in meiotic cells by regulating multiple DNA repair pathways.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
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
50
Issue of the periodical within the volume
21
Country of publishing house
GB - UNITED KINGDOM
Number of pages
18
Pages from-to
12291-12308
UT code for WoS article
000894104000001
EID of the result in the Scopus database
999