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


Authors: Dray, E.; Dunlop, M. H.; Kauppi, L.; San Filippo, J.; Wiese, C.; Tsai, M. S.; Begovic, S.; Schild, D.; Jasin, M.; Keeney, S.; Sung, P.
Article Title: Molecular basis for enhancement of the meiotic DMC1 recombinase by RAD51 associated protein 1 (RAD51AP1)
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.
Keywords: adolescent; protein expression; unclassified drug; dna-binding proteins; nonhuman; protein localization; animal cell; dna recombination; mouse; meiosis; animals; cell cycle proteins; mice; spermatocytes; animal tissue; homologous recombination; complex formation; dna repair; protein protein interaction; animal experiment; protein binding; nuclear proteins; chromatin; carrier proteins; protein transport; mutant proteins; nucleic acid conformation; chromosome pairing; protein isoforms; oligonucleotides; rad51 recombinase; synapse; genomic stability; recombinases; recombinase; meiotic proteins; dmc1 recombinase; rad51 associated protein 1
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 108
Issue: 9
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2011-03-01
Start Page: 3560
End Page: 3565
Language: English
DOI: 10.1073/pnas.1016454108
PUBMED: 21307306
PROVIDER: scopus
PMCID: PMC3048120
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 23 June 2011" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Scott N Keeney
    113 Keeney
  2. Liisa Hannele Kauppi
    10 Kauppi
  3. Maria Jasin
    224 Jasin