Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (282K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (12)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Hall, M. C.
Right arrow Articles by Kunkel, T. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hall, M. C.
Right arrow Articles by Kunkel, T. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2003, Vol. 31, No. 8 2025-2034
© 2003 Oxford University Press

DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch repair

Mark C. Hall1, Polina V. Shcherbakova1, John M. Fortune1, Christoph H. Borchers2, J. Michael Dial2, Kenneth B. Tomer2 and Thomas A. Kunkel1,2

1 Laboratory of Molecular Genetics and 2 Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Mark C. Hall, Christoph H. Borchers and J. Michael Dial, Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA

The yeast Mlh1–Pms1 heterodimer required for mismatch repair (MMR) binds to DNA. Here we map DNA binding to N-terminal fragments of Mlh1 and Pms1. We demonstrate that Mlh1 and Pms1 N-terminal domains (NTDs) independently bind to double-stranded and single-stranded DNA, in the absence of dimerization and with different affinities. Full-length Mlh1p alone, which can homodimerize, also binds to DNA. Substituting conserved positively charged amino acids in Mlh1 produces mutator phenotypes in a haploid yeast strain characteristic of reduced MMR. These substitutions strongly reduce DNA binding by the Mlh1 NTD and, to a lesser extent, they also reduce DNA binding by full-length Mlh1 and the Mlh1–Pms1 heterodimer. Replacement of a homologous Pms1 residue has a much smaller effect on mutation rate and does not reduce DNA binding. The results demonstrate that NTDs of yeast Mlh1 and Pms1 contain independent DNA binding sites and they suggest that the C-terminal region of Mlh1p may also contribute to DNA binding. The differential mutator effects and binding properties observed here further suggest that Mlh1 and Pms1 differ in their interactions with DNA. Finally, the results are consistent with the hypothesis that DNA binding by Mlh1 is important for MMR.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
G. Plotz, C. Welsch, L. Giron-Monzon, P. Friedhoff, M. Albrecht, A. Piiper, R. M. Biondi, T. Lengauer, S. Zeuzem, and J. Raedle
Mutations in the MutS{alpha} interaction interface of MLH1 can abolish DNA mismatch repair
Nucleic Acids Res., December 2, 2006; 34(22): 6574 - 6586.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. W. Matson and A. B. Robertson
The UvrD helicase and its modulation by the mismatch repair protein MutL
Nucleic Acids Res., September 10, 2006; 34(15): 4089 - 4097.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Robertson, S. R. Pattishall, and S. W. Matson
The DNA Binding Activity of MutL Is Required for Methyl-directed Mismatch Repair in Escherichia coli
J. Biol. Chem., March 31, 2006; 281(13): 8399 - 8408.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Erdeniz, S. Dudley, R. Gealy, S. Jinks-Robertson, and R. M. Liskay
Novel PMS1 Alleles Preferentially Affect the Repair of Primer Strand Loops during DNA Replication
Mol. Cell. Biol., November 1, 2005; 25(21): 9221 - 9231.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.