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Nucleic Acids Research Advance Access published online on November 11, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp976
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genome Integrity, Repair and Replication

Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin

Christina Bauerschmidt1, Cecilia Arrichiello2, Susanne Burdak-Rothkamm2, Michael Woodcock1,2, Mark A. Hill1, David L. Stevens1,3 and Kai Rothkamm1,2,3,*

1Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, 2Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR and 3Health Protection Agency, Radiation Protection Division, Chilton, Didcot, OX11 0RQ, UK

*To whom correspondence should be addressed. Tel: +44-1235-822700; Fax: +44-1235-833891; Email: kai.rothkamm{at}hpa.org.uk

Received June 10, 2009. Revised September 21, 2009. Accepted October 14, 2009.

The cohesin protein complex holds sister chromatids together after synthesis until mitosis. It also contributes to post-replicative DNA repair in yeast and higher eukaryotes and accumulates at sites of laser-induced damage in human cells. Our goal was to determine whether the cohesin subunits SMC1 and Rad21 contribute to DNA double-strand break repair in X-irradiated human cells in the G2 phase of the cell cycle. RNA interference-mediated depletion of SMC1 sensitized HeLa cells to X-rays. Repair of radiation-induced DNA double-strand breaks, measured by {gamma}H2AX/53BP1 foci analysis, was slower in SMC1- or Rad21-depleted cells than in controls in G2 but not in G1. Inhibition of the DNA damage kinase DNA-PK, but not ATM, further inhibited foci loss in cohesin-depleted cells in G2. SMC1 depletion had no effect on DNA single-strand break repair in either G1 or late S/G2. Rad21 and SMC1 were recruited to sites of X-ray-induced DNA damage in G2-phase cells, but not in G1, and only when DNA damage was concentrated in subnuclear stripes, generated by partially shielded ultrasoft X-rays. Our results suggest that the cohesin complex contributes to cell survival by promoting the repair of radiation-induced DNA double-strand breaks in G2-phase cells in an ATM-dependent pathway.


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