Published online 10 August 2005
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Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage
1Department of Orthopedics, Graduate School of Medicine, Osaka University Osaka, Japan 2Department of Radiation Genetics, Faculty of Medicine, Kyoto University Sakyo-ku, Kyoto, Japan 3CREST, Japan Science and Technology Saitama, Japan 4Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University Higashiyama-ku, Kyoto, Japan
*To whom correspondence should be addressed. Tel: +81 75 753 4410; Fax: +81 75 753 4419; Email: yamazoe{at}rg.med.kyoto-u.ac.jp
Received May 6, 2005. Revised July 26, 2005. Accepted July 26, 2005.
Metazoan Rad51 plays a central role in homologous DNA recombination, and its activity is controlled by a number of Rad51 cofactors. These include five Rad51 paralogs, Rad51B, Rad51C, Rad51D, XRCC2 and XRCC3. We previously hypothesized that all five paralogs participate collaboratively in repair. However, this idea was challenged by the biochemical identification of two independent complexes composed of either Rad51B/C/D/XRCC2 or Rad51C/XRCC3. To investigate if this biochemical finding is matched by genetic interactions, we made double mutants in either the same complex (rad51b/rad51d) or in both complexes (xrcc3/rad51d). In agreement with the biochemical findings the double deletion involving both complexes had an additive effect on the sensitivity to camptothecin and cisplatin. The double deletion of genes in the same complex, on the other hand, did not further increase the sensitivity to these agents. Conversely, all mutants tested displayed comparatively mild sensitivity to 
-irradiation and attenuated -irradiation-induced Rad51 foci formation. Thus, in accord with our previous conclusion, all paralogs appear to collaboratively facilitate Rad51 action. In conclusion, our detailed genetic study reveals a complex interplay between the five Rad51 paralogs and suggests that some of the Rad51 paralogs can separately operate in later step of homologous recombination.
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