FIGL1 and its novel partner FLIP form a conserved complex that regulates homologous recombination

PLoS Genet. 2018 Apr 2;14(4):e1007317. doi: 10.1371/journal.pgen.1007317. eCollection 2018 Apr.

Abstract

Homologous recombination is central to repair DNA double-strand breaks, either accidently arising in mitotic cells or in a programed manner at meiosis. Crossovers resulting from the repair of meiotic breaks are essential for proper chromosome segregation and increase genetic diversity of the progeny. However, mechanisms regulating crossover formation remain elusive. Here, we identified through genetic and protein-protein interaction screens FIDGETIN-LIKE-1 INTERACTING PROTEIN (FLIP) as a new partner of the previously characterized anti-crossover factor FIDGETIN-LIKE-1 (FIGL1) in Arabidopsis thaliana. We showed that FLIP limits meiotic crossover together with FIGL1. Further, FLIP and FIGL1 form a protein complex conserved from Arabidopsis to human. FIGL1 interacts with the recombinases RAD51 and DMC1, the enzymes that catalyze the DNA strand exchange step of homologous recombination. Arabidopsis flip mutants recapitulate the figl1 phenotype, with enhanced meiotic recombination associated with change in counts of DMC1 and RAD51 foci. Our data thus suggests that FLIP and FIGL1 form a conserved complex that regulates the crucial step of strand invasion in homologous recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / classification
  • ATPases Associated with Diverse Cellular Activities / genetics*
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Arabidopsis / genetics
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / classification
  • Arabidopsis Proteins / genetics*
  • Arabidopsis Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Homologous Recombination*
  • Microtubule-Associated Proteins / classification
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Multiprotein Complexes / metabolism
  • Mutation
  • Nuclear Proteins / classification
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phylogeny
  • Protein Binding
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Rec A Recombinases / genetics
  • Rec A Recombinases / metabolism
  • Two-Hybrid System Techniques

Substances

  • Arabidopsis Proteins
  • Cell Cycle Proteins
  • FLIP protein, Arabidopsis
  • Microtubule-Associated Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • ATDMC1 protein, Arabidopsis
  • ATRAD51 protein, Arabidopsis
  • Rad51 Recombinase
  • Rec A Recombinases
  • ATPases Associated with Diverse Cellular Activities
  • FIGL1 protein, Arabidopsis

Grant support

This work was funded by the European Research Council Grant ERC 2011 StG 281659 (MeioSight), the Schlumberger Foundation for Education and Research (FSER) and the Simone et Cino del DUCA fundation/Institut de France. RG was supported by the French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-01]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.