Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

Journal Article · Wed Apr 11 04:00:00 EDT 2007 · Molecular Cell

DOI:https://doi.org/10.1016/j.molcel.2007.08.027· OSTI ID:932500

Wiese, Claudia; Dray, Eloise; Groesser, Torsten; San Filippo, Joseph; Shi, Idina; Collins, David W; Tsai, Miaw-Sheue; Williams, Gareth; Rydberg, Bjorn; Sung, Patrick; Schild, David

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) 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. 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 dsDNA and RAD51, and it 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 the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director, Office of Science; National Aeronautics andSpace Administration
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 932500
• Report Number(s): LBNL--63697
• Journal Information: Molecular Cell, Journal Name: Molecular Cell Journal Issue: 3 Vol. 28
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
CHROMATIDS
CHROMOSOMES
DNA
NEOPLASMS
NUCLEOPROTEINS
PROTEINS
RECOMBINATION
REPAIR
RNA
SENSITIVITY
STABILITY