@article{ec7eb0c2465640799bfe2336d3c9d981,
title = "The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress",
abstract = "Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier (SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response.",
author = "Morris, {Joanna R.} and Chris Boutell and Melanie Keppler and Ruth Densham and Daniel Weekes and Amin Alamshah and Laura Butler and Yaron Galanty and Laurent Pangon and Tai Kiuchi and Tony Ng and Ellen Solomon",
note = "Funding Information: Acknowledgements We are grateful to V. De Laurenzi for the PIAS1 expression constructs, to R. Hay for His-SUMO1 and His-SUMO2 cells, to D. Durocher for anti-RNF168 antibody, to G. Stewart for discussions and S. Jackson for sharing results before publication. The work was supported by grants from Breast Cancer Campaign (to J.R.M., A.A., #SF06, and L.B., #06NovPHD13Morris), Cancer Research UK (to R.D., #C8820/A9494), the Medical Research Council (to E.S. and D.W., #6900577, and C.B.), the Richard Dimbleby Cancer Fund to King{\textquoteright}s College London (to M.K. and T.N.) and Breakthrough Breast Cancer (to T.K). Multiphoton FLIM systems and acquisition/analysis software were built by S. Ameer-Beg, P. Barber and B. Vojnovic, with support from MRC Co-operative Group Grant G0100152 #56891 and UK Research Councils Basic Technology Research Programme Grant GR/R87901/01.",
year = "2009",
month = dec,
day = "17",
doi = "10.1038/nature08593",
language = "English",
volume = "462",
pages = "886--890",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7275",
}
