Recruitment of MRE-11 to complex DNA damage is modulated by meiosis-specific chromosome organization

Harrell, Kailey; Day, Madison; Smolikove, Sarit

doi:10.1016/j.mrfmmm.2021.111743

Cited by 2 publications

(1 citation statement)

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“…To assess whether aberrant RAD-51 loading was caused by perturbations in any of these steps, we analysed localization of i) DSB-1, required for normal DSB induction, ii) MRE-11 and RAD-50, both belonging to the MRN/X complex and iii) BRC-2. We employed available tools for the analysis of MRE-11 ( 38 ), while functional RAD-50, DSB-1 and BRC-2 tagged lines ( Supplementary Figure S2A-B ) were generated by CRISPR/Cas9 for this study.…”

Section: Resultsmentioning

confidence: 99%

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

Trivedi

Blazícková

Silva

2022

Nucleic Acids Research

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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.

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Section: Resultsmentioning

confidence: 99%