Molecular basis for enhancement of the meiotic DMC1 recombinase by RAD51 associated protein 1 (RAD51AP1)

Eloïse Dray, Myun Hwa Dunlop, Liisa Kauppi, Joseph San Filippo, Claudia Wiese, Miaw Sheue Tsai, Sead Begovic, David Schild, Maria Jasin, Scott Keeney, Patrick Sung

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 associated protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex-DNA partner and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional cooperation is dependent on complex formation between DMC1 and RAD51AP1 and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci colocalize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.

Original languageEnglish (US)
Pages (from-to)3560-3565
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number9
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Keywords

  • DNA repair
  • Genomic stability
  • Meiotic proteins

ASJC Scopus subject areas

  • General

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