This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Studamire, B.
Right arrow Articles by Alani, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Studamire, B.
Right arrow Articles by Alani, E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 1999, p. 7558-7567, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Separation-of-Function Mutations in Saccharomyces cerevisiae MSH2 That Confer Mismatch Repair Defects but Do Not Affect Nonhomologous-Tail Removal during Recombination

Barbara Studamire,1 Gavrielle Price,1 Neal Sugawara,2 James E. Haber,2 and Eric Alani1,*

Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853-2703,1 and Rosenstiel Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02254-91102

Received 13 April 1999/Returned for modification 10 June 1999/Accepted 29 July 1999

Yeast Msh2p forms complexes with Msh3p and Msh6p to repair DNA mispairs that arise during DNA replication. In addition to their role in mismatch repair (MMR), the MSH2 and MSH3 gene products are required to remove 3' nonhomologous DNA tails during genetic recombination. The mismatch repair genes MSH6, MLH1, and PMS1, whose products interact with Msh2p, are not required in this process. We have identified mutations in MSH2 that do not disrupt genetic recombination but confer a strong defect in mismatch repair. Twenty-four msh2 mutations that conferred a dominant negative phenotype for mismatch repair were isolated. A subset of these mutations mapped to residues in Msh2p that were analogous to mutations identified in human nonpolyposis colorectal cancer msh2 kindreds. Approximately half of the these MMR-defective mutations retained wild-type or nearly wild-type activity for the removal of nonhomologous DNA tails during genetic recombination. The identification of mutations in MSH2 that disrupt mismatch repair without affecting recombination provides a first step in dissecting the Msh-effector protein complexes that are thought to play different roles during DNA repair and genetic recombination.

* Corresponding author. Mailing address: Department of Molecular Biology and Genetics, Cornell University, 459 Biotechnology Building, Ithaca, NY 14853-2703. Phone: (607) 254-4811. Fax: (607) 255-6249. E-mail: eea3{at}cornell.edu.

Molecular and Cellular Biology, November 1999, p. 7558-7567, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Pogorzala, L., Mookerjee, S., Sia, E. A. (2009). Evidence That Msh1p Plays Multiple Roles in Mitochondrial Base Excision Repair. Genetics 182: 699-709 [Abstract] [Full Text]  
  • Nicholson, A., Fabbri, R. M., Reeves, J. W., Crouse, G. F. (2006). The Effects of Mismatch Repair and RAD1 Genes on Interchromosomal Crossover Recombination in Saccharomyces cerevisiae. Genetics 173: 647-659 [Abstract] [Full Text]  
  • Goldfarb, T., Alani, E. (2005). Distinct Roles for the Saccharomyces cerevisiae Mismatch Repair Proteins in Heteroduplex Rejection, Mismatch Repair and Nonhomologous Tail Removal. Genetics 169: 563-574 [Abstract] [Full Text]  
  • Kovtun, I.V., Thornhill, A.R., McMurray, C.T. (2004). Somatic deletion events occur during early embryonic development and modify the extent of CAG expansion in subsequent generations. Hum Mol Genet 13: 3057-3068 [Abstract] [Full Text]  
  • Ellison, A. R., Lofing, J., Bitter, G. A. (2004). Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain. Nucleic Acids Res 32: 5321-5338 [Abstract] [Full Text]  
  • Sugawara, N., Goldfarb, T., Studamire, B., Alani, E., Haber, J. E. (2004). Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1. Proc. Natl. Acad. Sci. USA 101: 9315-9320 [Abstract] [Full Text]  
  • Parc, Y, Boisson, C, Thomas, G, Olschwang, S (2003). Cancer risk in 348 French MSH2 or MLH1 gene carriers. J. Med. Genet. 40: 208-213 [Full Text]  
  • Sia, E. A., Dominska, M., Stefanovic, L., Petes, T. D. (2001). Isolation and Characterization of Point Mutations in Mismatch Repair Genes That Destabilize Microsatellites in Yeast. Mol. Cell. Biol. 21: 8157-8167 [Abstract] [Full Text]  
  • Xie, Y., Liu, Y., Argueso, J. L., Henricksen, L. A., Kao, H.-I, Bambara, R. A., Alani, E. (2001). Identification of rad27 Mutations That Confer Differential Defects in Mutation Avoidance, Repeat Tract Instability, and Flap Cleavage. Mol. Cell. Biol. 21: 4889-4899 [Abstract] [Full Text]  
  • Evans, E., Alani, E. (2000). Roles for Mismatch Repair Factors in Regulating Genetic Recombination. Mol. Cell. Biol. 20: 7839-7844 [Full Text]  
  • Sokolsky, T., Alani, E. (2000). EXO1 and MSH6 Are High-Copy Suppressors of Conditional Mutations in the MSH2 Mismatch Repair Gene of Saccharomyces cerevisiae. Genetics 155: 589-599 [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»