Promotion of Homologous Recombination and Genomic Stability by RAD51AP1 via RAD51 Recombinase Enhancement

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 cel...

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Bibliographic Details
Published in:Molecular cell 2007-11, Vol.28 (3), p.482-490
Main Authors: Wiese, Claudia, Dray, Eloïse, Groesser, Torsten, San Filippo, Joseph, Shi, Idina, Collins, David W., Tsai, Miaw-Sheue, Williams, Gareth J., Rydberg, Bjorn, Sung, Patrick, Schild, David
Format: Article
Language:English
Subjects:
Chromatids - metabolism
DNA
DNA Breaks
DNA Damage
DNA Repair
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Electrophoretic Mobility Shift Assay
Genomic Instability
HeLa Cells
Humans
Mutation
Nucleic Acid Conformation
Rad51 Recombinase - metabolism
Recombination, Genetic
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Summary: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2007.08.027