PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Nucleic acids research

ISSN

0305-1048

e-ISSN

1362-4962

Svazek periodika

50

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

18

Strana od-do

12291-12308

Kód UT WoS článku

000894104000001

EID výsledku v databázi Scopus

999