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 Harrington, J. M.
Right arrow Articles by Kolodner, R. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harrington, J. M.
Right arrow Articles by Kolodner, R. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2007, p. 6546-6554, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00855-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Saccharomyces cerevisiae Msh2-Msh3 Acts in Repair of Base-Base Mispairs{triangledown} ,{dagger}

Jill M. Harrington and Richard D. Kolodner*

Ludwig Institute for Cancer Research, Departments of Medicine and Cellular and Molecular Medicine, and Cancer Center, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0669

Received 15 May 2007/ Returned for modification 15 June 2007/ Accepted 9 July 2007

DNA mismatch repair is thought to act through two subpathways involving the recognition of base-base and insertion/deletion mispairs by the Msh2-Msh6 heterodimer and the recognition of insertion/deletion mispairs by the Msh2-Msh3 heterodimer. Here, through genetic and biochemical approaches, we describe a previously unidentified role of the Msh2-Msh3 heterodimer in the recognition of base-base mispairs and the suppression of homology-mediated duplication and deletion mutations. Saccharomyces cerevisiae msh3 mutants did not show an increase in the rate of base substitution mutations by the CAN1 forward mutation assay compared to the rate for the wild type but did show an altered spectrum of base substitution mutations, including an increased accumulation of base pair changes from GC to CG and from AT to TA; msh3 mutants also accumulated homology-mediated duplication and deletion mutations. The mutation spectrum of mlh3 mutants paralleled that of msh3 mutants, suggesting that the Mlh1-Mlh3 heterodimer may also play a role in the repair of base-base mispairs and in the suppression of homology-mediated duplication and deletion mutations. Mispair binding analysis with purified Msh2-Msh3 and DNA substrates derived from CAN1 sequences found to be mutated in vivo demonstrated that Msh2-Msh3 exhibited robust binding to specific base-base mispairs that was consistent with functional mispair binding.

* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0669. Phone: (858) 534-7802, ext. 7804. Fax: (858) 534-7750. E-mail: rkolodner{at}ucsd.edu

{triangledown} Published ahead of print on 16 July 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, September 2007, p. 6546-6554, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00855-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tian, L., Gu, L., Li, G.-M. (2009). Distinct Nucleotide Binding/Hydrolysis Properties and Molar Ratio of MutS{alpha} and MutS{beta} Determine Their Differential Mismatch Binding Activities. J. Biol. Chem. 284: 11557-11562 [Abstract] [Full Text]  
  • Lehner, K., Jinks-Robertson, S. (2009). The mismatch repair system promotes DNA polymerase {zeta}-dependent translesion synthesis in yeast. Proc. Natl. Acad. Sci. USA 106: 5749-5754 [Abstract] [Full Text]  
  • Hong, Z., Jiang, J., Hashiguchi, K., Hoshi, M., Lan, L., Yasui, A. (2008). Recruitment of mismatch repair proteins to the site of DNA damage in human cells. J. Cell Sci. 121: 3146-3154 [Abstract] [Full Text]  
  • Stone, J. E., Ozbirn, R. G., Petes, T. D., Jinks-Robertson, S. (2008). Role of Proliferating Cell Nuclear Antigen Interactions in the Mismatch Repair-Dependent Processing of Mitotic and Meiotic Recombination Intermediates in Yeast. Genetics 178: 1221-1236 [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»