Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination.

Abstract:

:During DNA double-strand break and replication fork repair by homologous recombination, the RAD51 recombinase catalyzes the DNA strand exchange reaction via a helical polymer assembled on single-stranded DNA, termed the presynaptic filament. Our published work has demonstrated a dual function of the SWI5-SFR1 complex in RAD51-mediated DNA strand exchange, namely, by stabilizing the presynaptic filament and maintaining the catalytically active ATP-bound state of the filament via enhancement of ADP release. In this study, we have strived to determine the basis for physical and functional interactions between Mus musculus SWI5-SFR1 and RAD51. We found that SWI5-SFR1 preferentially associates with the oligomeric form of RAD51. Specifically, a C-terminal domain within SWI5 contributes to RAD51 interaction. With specific RAD51 interaction defective mutants of SWI5-SFR1 that we have isolated, we show that the physical interaction is indispensable for the stimulation of the recombinase activity of RAD51. Our results thus help establish the functional relevance of the trimeric RAD51-SWI5-SFR1 complex and provide insights into the mechanistic underpinnings of homology-directed DNA repair in mammalian cells.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Su GC,Yeh HY,Lin SW,Chung CI,Huang YS,Liu YC,Lyu PC,Chi P

doi

10.1093/nar/gkw375

subject

Has Abstract

pub_date

2016-07-27 00:00:00

pages

6242-51

issue

13

eissn

0305-1048

issn

1362-4962

pii

gkw375

journal_volume

44

pub_type

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