Antagonism between BRCA2 and FIGL1 regulates homologous recombination

Nucleic Acids Res. 2019 Jun 4;47(10):5170-5180. doi: 10.1093/nar/gkz225.

Abstract

Homologous recombination (HR) maintains genome stability by promoting accurate DNA repair. Two recombinases, RAD51 and DMC1, are central to HR repair and form dynamic nucleoprotein filaments in vivo under tight regulation. However, the interplay between positive and negative regulators to control the dynamic assembly/disassembly of RAD51/DMC1 filaments in multicellular eukaryotes remains poorly characterized. Here, we report an antagonism between BRCA2, a well-studied positive mediator of RAD51/DMC1, and FIDGETIN-LIKE-1 (FIGL1), which we previously proposed as a negative regulator of RAD51/DMC1. Through forward genetic screen, we identified a mutation in one of the two Arabidopsis BRCA2 paralogs that suppresses the meiotic phenotypes of figl1. Consistent with the antagonistic roles of BRCA2 and FIGL1, the figl1 mutation in the brca2 background restores RAD51/DMC1 focus formation and homologous chromosome interaction at meiosis, and RAD51 focus formation in somatic cells. This study shows that BRCA2 and FIGL1 have antagonistic effects on the dynamics of RAD51/DMC1-dependent DNA transactions to promote accurate HR repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / antagonists & inhibitors*
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / antagonists & inhibitors*
  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / metabolism
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • DNA / chemistry
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Epistasis, Genetic*
  • Homologous Recombination*
  • Meiosis
  • Microtubule-Associated Proteins / antagonists & inhibitors*
  • Microtubule-Associated Proteins / metabolism
  • Models, Genetic
  • Mutation
  • Nucleoproteins / chemistry*
  • Phenotype
  • Rad51 Recombinase / chemistry
  • Rec A Recombinases / chemistry
  • Recombinational DNA Repair

Substances

  • AT4G00020 protein, Arabidopsis
  • AT5G01630 protein, Arabidopsis
  • Arabidopsis Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Microtubule-Associated Proteins
  • Nucleoproteins
  • DNA
  • ATDMC1 protein, Arabidopsis
  • ATRAD51 protein, Arabidopsis
  • Rad51 Recombinase
  • Rec A Recombinases
  • ATPases Associated with Diverse Cellular Activities
  • FIGL1 protein, Arabidopsis