| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print April 10, 2002
Institute of Medical Radiobiology, Zurich 8008
Corresponding Author: jiricny{at}imr.unizh.ch
The MutL family of mismatch repair proteins belongs to the GHKL class of ATPases, which contains also type II topoisomerases, HSP90 and histidine kinases. The nucleotide binding domains of these polypeptides are highly conserved, but this similarity has failed to help us understand the biological role of the ATPase activity of the MutL proteins in mismatch repair. hMutL
J. Biol. Chem, 10.1074/jbc.M108787200
Submitted on September 12, 2001
Revised on April 9, 2002
Accepted on April 10, 2002
Mutations within the hMLH1 and hPMS2 subunits of the human MutL
mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutS
is a heterodimer of the human MutL homologues hMLH1 and hPMS2 and we decided to exploit its asymmetry to study this function. We now show that although the two subunits contribute differently to the ATPase activity of the heterodimer, hMutL variants in which one subunit was able to bind – but not hydrolyze – ATP, displayed similarly reduced mismatch repair activities in vitro. In contrast, variants in which either subunit was unable to bind the nucleotide were inactive. Mutation of the catalytic sites of both subunits abolished repair without altering the ability of these peptides to interact with one another. As the binding of the nucleotide in hMutL was not required for the formation of ternary complexes with the mismatch recognition factor hMutS bound to a heteroduplex substrate, we propose that the ATPase activity of hMutL is required downstream from this process.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Avdievich, C. Reiss, S. J. Scherer, Y. Zhang, S. M. Maier, B. Jin, H. Hou Jr, A. Rosenwald, H. Riedmiller, R. Kucherlapati, et al. Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis PNAS, March 18, 2008; 105(11): 4247 - 4252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Fan, W. Wang, M. Zhu, J. Zhou, J. Peng, L. Xu, Z. Hua, X. Gao, and Y. Wang Analysis of hMLH1 Missense Mutations in East Asian Patients with Suspected Hereditary Nonpolyposis Colorectal Cancer Clin. Cancer Res., December 15, 2007; 13(24): 7515 - 7521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang and J. B. Hays Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision Nucleic Acids Res., November 29, 2007; 35(20): 6727 - 6739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. O. Knudsen, F. C. Nielsen, L. Vinther, R. Bertelsen, S. Holten-Andersen, S. E. Liberti, R. Hofstra, K. Kooi, and L. J. Rasmussen Nuclear localization of human DNA mismatch repair protein exonuclease 1 (hEXO1) Nucleic Acids Res., April 10, 2007; (2007) gkl1166v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Cannavo, B. Gerrits, G. Marra, R. Schlapbach, and J. Jiricny Characterization of the Interactome of the Human MutL Homologues MLH1, PMS1, and PMS2 J. Biol. Chem., February 2, 2007; 282(5): 2976 - 2986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 E. Cannavo, G. Marra, J. Sabates-Bellver, M. Menigatti, S. M. Lipkin, F. Fischer, P. Cejka, and J. Jiricny Expression of the MutL Homologue hMLH3 in Human Cells and its Role in DNA Mismatch Repair Cancer Res., December 1, 2005; 65(23): 10759 - 10766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Mendillo, D. J. Mazur, and R. D. Kolodner Analysis of the Interaction between the Saccharomyces cerevisiae MSH2-MSH6 and MLH1-PMS1 Complexes with DNA Using a Reversible DNA End-blocking System J. Biol. Chem., June 10, 2005; 280(23): 22245 - 22257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Ellison, J. Lofing, and G. A. Bitter Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain Nucleic Acids Res., October 8, 2004; 32(18): 5321 - 5338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Shaver and P. D. Sniegowski Spontaneously Arising mutL Mutators in Evolving Escherichia coli Populations Are the Result of Changes in Repeat Length J. Bacteriol., October 15, 2003; 185(20): 6076 - 6082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Plotz, J. Raedle, A. Brieger, J. Trojan, and S. Zeuzem N-terminus of hMLH1 confers interaction of hMutL{alpha} and hMutL{beta} with hMutS{alpha} Nucleic Acids Res., June 15, 2003; 31(12): 3217 - 3226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kondo, H. Suzuki, A. Horii, and S. Fukushige A Yeast Two-Hybrid Assay Provides a Simple Way to Evaluate the Vast Majority of hMLH1 Germ-Line Mutations Cancer Res., June 15, 2003; 63(12): 3302 - 3308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wu, J. L. Platt, and M. Cascalho Dimerization of MLH1 and PMS2 Limits Nuclear Localization of MutL{alpha} Mol. Cell. Biol., May 1, 2003; 23(9): 3320 - 3328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Argueso, A. W. Kijas, S. Sarin, J. Heck, M. Waase, and E. Alani Systematic Mutagenesis of the Saccharomyces cerevisiae MLH1 Gene Reveals Distinct Roles for Mlh1p in Meiotic Crossing Over and in Vegetative and Meiotic Mismatch Repair Mol. Cell. Biol., February 1, 2003; 23(3): 873 - 886. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
