Imperial College London
Portrait Picture

Professor David S. Rueda

Faculty of Medicine, Department of Infectious Disease

Chair in Molecular and Cellular Biophysics
 
 
 
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Contact

 

david.rueda Website

 
 
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Location

 

6.12DLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Belan:2021:10.1016/j.molcel.2020.12.020,
author = {Belan, O and Barroso, C and Kaczmarczyk, A and Anand, R and Federico, S and OReilly, N and Newton, MD and Maeots, E and Enchev, RI and Martinez-Perez, E and Rueda, DS and Boulton, SJ},
doi = {10.1016/j.molcel.2020.12.020},
journal = {Molecular Cell},
pages = {1058--1073.e7},
title = {Single-molecule analysis reveals cooperative stimulation of Rad51 filament nucleation and growth by mediator proteins},
url = {http://dx.doi.org/10.1016/j.molcel.2020.12.020},
volume = {81},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Homologous recombination (HR) is an essential DNA double-strand break (DSB) repair mechanism, which is frequently inactivated in cancer. During HR, RAD51 forms nucleoprotein filaments on RPA-coated, resected DNA and catalyzes strand invasion into homologous duplex DNA. How RAD51 displaces RPA and assembles into long HR-proficient filaments remains uncertain. Here, we employed single-molecule imaging to investigate the mechanism of nematode RAD-51 filament growth in the presence of BRC-2 (BRCA2) and RAD-51 paralogs, RFS-1/RIP-1. BRC-2 nucleates RAD-51 on RPA-coated DNA, whereas RFS-1/RIP-1 acts as a “chaperone” to promote 3′ to 5′ filament growth via highly dynamic engagement with 5′ filament ends. Inhibiting ATPase or mutation in the RFS-1 Walker box leads to RFS-1/RIP-1 retention on RAD-51 filaments and hinders growth. The rfs-1 Walker box mutants display sensitivity to DNA damage and accumulate RAD-51 complexes non-functional for HR in vivo. Our work reveals the mechanism of RAD-51 nucleation and filament growth in the presence of recombination mediators.
AU  - Belan,O
AU  - Barroso,C
AU  - Kaczmarczyk,A
AU  - Anand,R
AU  - Federico,S
AU  - OReilly,N
AU  - Newton,MD
AU  - Maeots,E
AU  - Enchev,RI
AU  - Martinez-Perez,E
AU  - Rueda,DS
AU  - Boulton,SJ
DO  - 10.1016/j.molcel.2020.12.020
EP  - 1073
PY  - 2021///
SN  - 1097-2765
SP  - 1058
TI  - Single-molecule analysis reveals cooperative stimulation of Rad51 filament nucleation and growth by mediator proteins
T2  - Molecular Cell
UR  - http://dx.doi.org/10.1016/j.molcel.2020.12.020
UR  - http://hdl.handle.net/10044/1/87782
VL  - 81
ER  -
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