Skip Navigation



Nucleic Acids Research Advance Access published online on June 23, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp538
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (1191K) Freely available
Right arrow Screen PDF (370K) Freely available
Right arrowOA All Versions of this Article:
37/15/5105    most recent
gkp538v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Ying, S.
Right arrow Articles by Bryant, H. E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ying, S.
Right arrow Articles by Bryant, H. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/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

BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells

Songmin Ying1, Katie Myers1, Sarah Bottomley1, Thomas Helleday2 and Helen E. Bryant1,*

1The Institute for Cancer Studies, University of Sheffield, Sheffield S10 2RX and 2Gray Institute for Radiation Oncology & Biology, University of Oxford, Oxford, OX3 7DQ, UK

*To whom correspondence should be addressed. Tel: +44 114 2712993; Fax: +44 114 2795320; Email: h.bryant{at}sheffield.ac.uk

Received March 13, 2009. Revised June 8, 2009. Accepted June 8, 2009.

Arsenic exposure constitutes one of the most widespread environmental carcinogens, and is associated with increased risk of many different types of cancers. Here we report that arsenite (As[III]) can induce both replication-dependent DNA double-strand breaks (DSB) and homologous recombination (HR) at doses as low as 5 µM (0.65 mg/l), which are within the typical doses often found in drinking water in contaminated areas. We show that the production of DSBs is dependent on active replication and is likely to be the result of conversion of a DNA single-strand break (SSB) into a toxic DSB when encountered by a replication fork. We demonstrate that HR is required for the repair of these breaks and show that a functional HR pathway protects against As[III]-induced cytotoxicity. In addition, BRCA2-deficient cells are sensitive to As[III] and we suggest that As[III] could be exploited as a therapy for HR-deficient tumours such as BRCA1 and BRCA2 mutated breast and ovarian cancers.

Present address: Songmin Ying, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.