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Mol Cell. 2007 Nov 9;28(3):482-90.

Promotion of homologous recombination and genomic stability by RAD51AP1 via RAD51 recombinase enhancement.

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1
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Abstract

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand-pairing step in HR. RAD51 associated protein 1 (RAD51AP1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress, and RAD51AP1 is epistatic to the HR protein XRCC3. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA-damaging treatment. Purified RAD51AP1 binds both dsDNA and a D loop structure and, only when able to interact with RAD51, greatly stimulates the RAD51-mediated D loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

PMID:
17996711
PMCID:
PMC2169287
DOI:
10.1016/j.molcel.2007.08.027
[Indexed for MEDLINE]
Free PMC Article
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