RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination.
Homologous recombination is essential for preserving genome integrity. Joining of homologous DNA molecules through strand exchange, a pivotal step in recombination, is mediated by RAD51. Here, we identify RAD51AP1 as a RAD51 accessory protein that specifically stimulates joint molecule formation through the combination of structure-specific DNA binding and physical contact with RAD51. At the cellular level, we show that RAD51AP1 is required to protect cells from the adverse effects of DNA double-strand break-inducing agents. At the biochemical level, we show that RAD51AP1 has a selective affinity for branched-DNA structures that are obligatory intermediates during joint molecule formation. Our results highlight the importance of structural transitions in DNA as control points in recombination. The affinity of RAD51AP1 for the central protein and DNA intermediates of recombination confers on it the ability to control the preservation of genome integrity at a number of critical mechanistic steps.
Modesti
Mauro
M
Department of Cell Biology and Genetics, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. mmodesti@ibsm.cnrs-mrs.fr
Budzowska
Magda
M
Baldeyron
Céline
C
Demmers
Jeroen A A
JA
Ghirlando
Rodolfo
R
Kanaar
Roland
R
D001483:Base Sequence; D004249:DNA Damage; D045566:DNA, Cruciform / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic / Q000502:physiology*
D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; C110410:RAD51AP1 protein, human; D016601:RNA-Binding Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase