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; Jitka BLAŽÍČKOVÁ and Nicola SILVA

Edition

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

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 14.900

Marked to be transferred to RIV

Yes

RIV identification code

RIV/00216224:14110/22:00128165

Organization unit

Faculty of Medicine

Keywords in English

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

Abstract

In the original language

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

90129, large research infrastructures

Name: Czech-BioImaging II

Cite

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

@article{2248041,
   author = {Trivedi, Shalini and Blažíčková, Jitka and Silva, Nicola},
   article_location = {Oxford},
   article_number = {21},
   doi = {https://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://doi.org/10.1093/nar/gkac1153.

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