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

J 2022

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

TRIVEDI, Shalini, Jitka BLAŽÍČKOVÁ and Nicola SILVA

Basic information

Original name

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

Authors

TRIVEDI, Shalini (356 India, belonging to the institution), Jitka BLAŽÍČKOVÁ (203 Czech Republic, belonging to the institution) and Nicola SILVA (380 Italy, guarantor, belonging to the institution)

Edition

Nucleic acids research, Oxford, Oxford University Press, 2022, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 14.900

RIV identification code

RIV/00216224:14110/22:00128165

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1093/nar/gkac1153

UT WoS

000894104000001

Keywords in English

PARG; BRCA1–BARD1; DNA repair pathway choice; gametogenesis

Abstract

V originále

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.

Links

GA20-08819S, research and development project

Name: Pochopení úlohy PARG při podpoře tvorby a oprav dvouřetězcových zlomů DNA v meióze

Investor: Czech Science Foundation

LM2018129, research and development project

Name: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

TRIVEDI, Shalini, Jitka BLAŽÍČKOVÁ and Nicola SILVA. PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis. Nucleic acids research. Oxford: Oxford University Press, 2022, vol. 50, No 21, p. 12291-12308. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkac1153.

@article{2248041,
   author = {Trivedi, Shalini and Blažíčková, Jitka and Silva, Nicola},
   article_location = {Oxford},
   article_number = {21},
   doi = {http://dx.doi.org/10.1093/nar/gkac1153},
   keywords = {PARG; BRCA1–BARD1; DNA repair pathway choice; gametogenesis},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic acids research},
   title = {PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis},
   url = {https://academic.oup.com/nar/article/50/21/12291/6882108?login=true},
   volume = {50},
   year = {2022}
}

TY  - JOUR
ID  - 2248041
AU  - Trivedi, Shalini - Blažíčková, Jitka - Silva, Nicola
PY  - 2022
TI  - PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis
JF  - Nucleic acids research
VL  - 50
IS  - 21
SP  - 12291-12308
EP  - 12291-12308
PB  - Oxford University Press
SN  - 03051048
KW  - PARG
KW  - BRCA1–BARD1
KW  - DNA repair pathway choice
KW  - gametogenesis
UR  - https://academic.oup.com/nar/article/50/21/12291/6882108?login=true
N2  - 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.
ER  -

TRIVEDI, Shalini, Jitka BLAŽÍČKOVÁ and Nicola SILVA. PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis. \textit{Nucleic acids research}. Oxford: Oxford University Press, 2022, vol.~50, No~21, p.~12291-12308. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkac1153.

Detailed Information on Publication Record