Published online 13 July 2006
© 2006 The Author(s)
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Dpb11, the budding yeast homolog of TopBP1, functions with the checkpoint clamp in recombination repair
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan 1 Tohoku University 21st Century COE Program Comprehensive Research and Education Center for Planning of Drug development and Clinical Evaluation Sendai, Miyagi 980-88578, Japan
*To whom correspondence should be addressed. Tel: +22 795 6875; Fax: +22 795 6873; Email: seki{at}mail.pharm.tohoku.ac.jp
Received February 20, 2006. Revised May 11, 2006. Accepted May 17, 2006.
Dpb11 is required for the loading of DNA polymerases
and
on to DNA in chromosomal DNA replication and interacts with the DNA damage checkpoint protein Ddc1 in Saccharomyces cerevisiae. The interaction between the homologs of Dpb11 and Ddc1 in human cells and fission yeast is thought to reflect their involvement in the checkpoint response. Here we show that dpb11-1 cells, carrying a mutated Dpb11 that cannot interact with Ddc1, are defective in the repair of methyl methanesulfonate (MMS)-induced DNA damage but not in the DNA damage checkpoint at the permissive temperature. Epistatic analyses suggested that Dpb11 is involved in the Rad51/Rad52-dependent recombination pathway. Ddc1 as well as Dpb11 were required for homologous recombination induced by MMS. Moreover, we found the in vivo association of Dpb11 and Ddc1 with not only the HO-induced double-strand break (DSB) site at MAT locus but also the donor sequence HML during homologous recombination between MAT and HML. Rad51 was required for their association with the HML donor locus, but not with DSB site at the MAT locus. In addition, the association of Dpb11 with the MAT and HML locus after induction of HO-induced DSB was dependent on Ddc1. These results indicate that, besides the involvement in the replication and checkpoint, Dpb11 functions with Ddc1 in the recombination repair process itself.
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