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@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.
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