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

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

Research output: Contribution to journalJournal articleResearchpeer-review

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 theHRprotein 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 DNAdamaging 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.
Original languageEnglish
JournalMolecular Cell
Volume28
Pages (from-to)482–490
ISSN1097-2765
DOIs
Publication statusPublished - 2007
Externally publishedYes

Cite this

Wiese, C., Dray, E., Groesser, T., Filippo, J. S., Shi, I., Collins, D. W., Tsai, M-S., Williams, G. J., Rydberg, B., Sung, P., & Schild, D. (2007). Promotion of Homologous Recombination and Genomic Stability by RAD51AP1 via RAD51 Recombinase Enhancement. Molecular Cell, 28, 482–490. https://doi.org/10.1016/j.molcel.2007.08.027