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Nucleic Acids Research Advance Access originally published online on October 8, 2008
Nucleic Acids Research 2008 36(20):6406-6417; doi:10.1093/nar/gkn686
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Nucleic Acids Research, 2008, Vol. 36, No. 20 6406-6417
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genome integrity, repair and replication

Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1

Wei He1,2, Yun Zhao1,2, Chunbo Zhang1,3, Lili An1,2, Zhishang Hu1,2, Yuheng Liu1,2, Lu Han1,2, Lijun Bi4, Zhensheng Xie5, Peng Xue5, Fuquan Yang5 and Haiying Hang1,2,*

1National Laboratory of Biomacromolecules, 2Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, 3College of Life Sciences, Capital Normal University, Beijing 100037, 4Center for Systems Biology and 5Proteomics Platform, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 and China

*To whom correspondence should be addressed. Tel: +86 10 6488 8473; Fax: +86 10 6488 8473; Email: hh91{at}sun5.ibp.ac.cn

Correspondence may also be addressed to Fuquan Yang. Tel: +86 10 6488 8581; Fax: +86 10 6488 8581; Email: fqyang{at}sun5.ibp.ac.cn

Received July 5, 2008. Revised September 24, 2008. Accepted September 24, 2008.

Rad9 is conserved from yeast to humans and plays roles in DNA repair (homologous recombination repair, and base-pair excision repair) and cell cycle checkpoint controls. It has not previously been reported whether Rad9 is involved in DNA mismatch repair (MMR). In this study, we have demonstrated that both human and mouse Rad9 interacts physically with the MMR protein MLH1. Disruption of the interaction by a single-point mutation in Rad9 leads to significantly reduced MMR activity. This disruption does not affect S/M checkpoint control and the first round of G2/M checkpoint control, nor does it alter cell sensitivity to UV light, gamma rays or hydroxyurea. Our data indicate that Rad9 is an important factor in MMR and carries out its MMR function specifically through interaction with MLH1.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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