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Molecular and Cellular Biology, April 2005, p. 3127-3139, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3127-3139.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

RAD-51-Dependent and -Independent Roles of a Caenorhabditis elegans BRCA2-Related Protein during DNA Double-Strand Break Repair{dagger},{ddagger}

Julie S. Martin, Nicole Winkelmann, Mark I. R. Petalcorin, Michael J. McIlwraith, and Simon J. Boulton*

Clare Hall Laboratories, London Research Institute, Cancer Research UK, South Mimms, Hertfordshire, United Kingdom

Received 26 November 2004/ Returned for modification 27 December 2004/ Accepted 24 January 2005

The BRCA2 tumor suppressor is implicated in DNA double-strand break (DSB) repair by homologous recombination (HR), where it regulates the RAD51 recombinase. We describe a BRCA2-related protein of Caenorhabditis elegans (CeBRC-2) that interacts directly with RAD-51 via a single BRC motif and that binds preferentially to single-stranded DNA through an oligonucleotide-oligosaccharide binding fold. Cebrc-2 mutants fail to repair meiotic or radiation-induced DSBs by HR due to inefficient RAD-51 nuclear localization and a failure to target RAD-51 to sites of DSBs. Genetic and cytological comparisons of Cebrc-2 and rad-51 mutants revealed fundamental phenotypic differences that suggest a role for Cebrc-2 in promoting the use of an alternative repair pathway in the absence of rad-51 and independent of nonhomologous end joining (NHEJ). Unlike rad-51 mutants, Cebrc-2 mutants also accumulate RPA-1 at DSBs, and abnormal chromosome aggregates that arise during the meiotic prophase can be rescued by blocking the NHEJ pathway. CeBRC-2 also forms foci in response to DNA damage and can do so independently of rad-51. Thus, CeBRC-2 not only regulates RAD-51 during HR but can also function independently of rad-51 in DSB repair processes.

* Corresponding author. Mailing address: Clare Hall Laboratories, London Research Institute, Cancer Research UK, Blanche Ln., South Mimms, Hertfordshire EN6 3LD, United Kingdom. Phone: 44 1707 625774. Fax: 44 208 269 3801. E-mail: simon.boulton{at}cancer.org.uk.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} We dedicate this work to the memory of Nicole Winkelmann.

Molecular and Cellular Biology, April 2005, p. 3127-3139, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3127-3139.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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