Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination.
Guan-Chin Su, Hsin-Yi Yeh, Sheng-Wei Lin, Chan-I Chung, Yu-Shan Huang, Yi-Chung Liu, Ping-Chiang Lyu, Peter Chi
Author Information
Guan-Chin Su: Institute of Biochemical Sciences, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.
Hsin-Yi Yeh: Institute of Biochemical Sciences, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.
Sheng-Wei Lin: Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
Chan-I Chung: Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
Yu-Shan Huang: National Synchrotron Radiation Research Center, No.101, Hsin-Ann Road, Hsinchu, Science Park, Hsinchu 30076, Taiwan.
Yi-Chung Liu: Institute of Population Sciences, National Health Research Institutes, NO. 35 Keyan, Road, Zhunan, Miaoli County 35053, Taiwan.
Ping-Chiang Lyu: Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Peter Chi: Institute of Biochemical Sciences, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan peterhchi@ntu.edu.tw.
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.
References
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