This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Martin, J. S.
Right arrow Articles by Boulton, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martin, J. S.
Right arrow Articles by Boulton, S. J.

 Previous Article  |  Next Article 

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.



This article has been cited by other articles:

  • Pauklin, S., Burkert, J. S., Martin, J., Osman, F., Weller, S., Boulton, S. J., Whitby, M. C., Petersen-Mahrt, S. K. (2009). Alternative Induction of Meiotic Recombination From Single-Base Lesions of DNA Deaminases. Genetics 182: 41-54 [Abstract] [Full Text]  
  • Zhou, Q., Kojic, M., Holloman, W. K. (2009). DNA-binding Domain within the Brh2 N Terminus Is the Primary Interaction Site for Association with DNA. J. Biol. Chem. 284: 8265-8273 [Abstract] [Full Text]  
  • Youds, J. L., Barber, L. J., Ward, J. D., Collis, S. J., O'Neil, N. J., Boulton, S. J., Rose, A. M. (2008). DOG-1 Is the Caenorhabditis elegans BRIP1/FANCJ Homologue and Functions in Interstrand Cross-Link Repair. Mol. Cell. Biol. 28: 1470-1479 [Abstract] [Full Text]  
  • Smolikov, S., Eizinger, A., Hurlburt, A., Rogers, E., Villeneuve, A. M., Colaiacovo, M. P. (2007). Synapsis-Defective Mutants Reveal a Correlation Between Chromosome Conformation and the Mode of Double-Strand Break Repair During Caenorhabditis elegans Meiosis. Genetics 176: 2027-2033 [Abstract] [Full Text]  
  • Petalcorin, M. I. R., Galkin, V. E., Yu, X., Egelman, E. H., Boulton, S. J. (2007). Stabilization of RAD-51-DNA filaments via an interaction domain in Caenorhabditis elegans BRCA2. Proc. Natl. Acad. Sci. USA 104: 8299-8304 [Abstract] [Full Text]  
  • Harris, J., Lowden, M., Clejan, I., Tzoneva, M., Thomas, J. H., Hodgkin, J., Ahmed, S. (2006). Mutator Phenotype of Caenorhabditis elegans DNA Damage Checkpoint Mutants. Genetics 174: 601-616 [Abstract] [Full Text]  
  • Clejan, I., Boerckel, J., Ahmed, S. (2006). Developmental Modulation of Nonhomologous End Joining in Caenorhabditis elegans. Genetics 173: 1301-1317 [Abstract] [Full Text]  
  • Saeki, H., Siaud, N., Christ, N., Wiegant, W. W., van Buul, P. P. W., Han, M., Zdzienicka, M. Z., Stark, J. M., Jasin, M. (2006). Suppression of the DNA repair defects of BRCA2-deficient cells with heterologous protein fusions. Proc. Natl. Acad. Sci. USA 103: 8768-8773 [Abstract] [Full Text]  
  • Dray, E., Siaud, N., Dubois, E., Doutriaux, M.-P. (2006). Interaction between Arabidopsis Brca2 and Its Partners Rad51, Dmc1, and Dss1. Plant Physiol. 140: 1059-1069 [Abstract] [Full Text]  
  • Kojic, M., Zhou, Q., Lisby, M., Holloman, W. K. (2006). Rec2 Interplay with both Brh2 and Rad51 Balances Recombinational Repair in Ustilago maydis. Mol. Cell. Biol. 26: 678-688 [Abstract] [Full Text]  
  • Proudfoot, C., McCulloch, R. (2005). Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation. Nucleic Acids Res 33: 6906-6919 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»