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 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.
Wiese
Claudia
C
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Dray
Eloïse
E
Groesser
Torsten
T
San Filippo
Joseph
J
Shi
Idina
I
Collins
David W
DW
Tsai
Miaw-Sheue
MS
Williams
Gareth J
GJ
Rydberg
Bjorn
B
Sung
Patrick
P
Schild
David
D
D002842:Chromatids / Q000378:metabolism; D053960:DNA Breaks; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009690:Nucleic Acid Conformation; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic
D004268:DNA-Binding Proteins; C110410:RAD51AP1 protein, human; D016601:RNA-Binding Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase