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Molecular and Cellular Biology, June 2008, p. 3639-3651, Vol. 28, No. 11
0270-7306/08/$08.00+0 doi:10.1128/MCB.01828-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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Yasuto Murayama,1,
Takatomi Yamada,2
Tomofumi Nakazaki,1
Yasuhiro Tsutsui,3
Kunihiro Ohta,2 and
Hiroshi Iwasaki1*
Division of Molecular and Cellular Biology, International Graduate School of Arts and Sciences, Yokohama City University, Suehiro-cho, Tsurumi, Yokohama, Kanagawa 230-0045,1 Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902,2 Division of Mutagenesis, National Institute of Genetics, Yata, Mishima, Shizuoka 411-8540, Japan3
Received 8 October 2007/ Returned for modification 13 November 2007/ Accepted 17 March 2008
The Schizosaccharomyces pombe nip1+/ctp1+ gene was previously identified as an slr (synthetically lethal with rad2) mutant. Epistasis analysis indicated that Nip1/Ctp1 functions in Rhp51-dependent recombinational repair, together with the Rad32 (spMre11)-Rad50-Nbs1 complex, which plays important roles in the early steps of DNA double-strand break repair. Nip1/Ctp1 was phosphorylated in asynchronous, exponentially growing cells and further phosphorylated in response to bleomycin treatment. Overproduction of Nip1/Ctp1 suppressed the DNA repair defect of an nbs1-s10 mutant, which carries a mutation in the FHA phosphopeptide-binding domain of Nbs1, but not of an nbs1 null mutant. Meiotic DNA double-strand breaks accumulated in the nip1/ctp1 mutant. The DNA repair phenotypes and epistasis relationships of nip1/ctp1 are very similar to those of the Saccharomyces cerevisiae sae2/com1 mutant, suggesting that Nip1/Ctp1 is a functional homologue of Sae2/Com1, although the sequence similarity between the proteins is limited to the C-terminal region containing the RHR motif. We found that the RxxL and CxxC motifs are conserved in Schizosaccharomyces species and in vertebrate CtIP, originally identified as a cofactor of the transcriptional corepressor CtBP. However, these two motifs are not found in other fungi, including Saccharomyces and Aspergillus species. We propose that Nip1/Ctp1 is a functional counterpart of Sae2/Com1 and CtIP.
Published ahead of print on 31 March 2008.
These two authors contributed equally to this work.
Present address: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
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