Human Molecular Genetics, 2002, Vol. 11, No. 15 1697-1706
© 2002 Oxford University Press
The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination
UMR CNRS/UNSA 6549, Faculté de Médecine, Av. de Valombrose, 06107 Nice cedex 2, France
Received February 13, 2002; Accepted May 15, 2002
The mismatch-repair (MMR) system plays a central role in maintaining genetic stability and requires evolutionarily conserved protein factors, including MutS and MutL homologs. Since the discovery of a link between the malfunction of post-replicative MMR and human cancers, a number of works have focused on the function of MutS and MutL homologs in the correction of replication errors. However, several MutS-like and MutL-like proteins also participate in meiotic recombination. The MutL homolog MLH3 has been recently identified in mammals. Several pieces of evidence support a role for this protein in post-replicative MMR. To investigate whether MLH3 also acts during meiotic recombination, we analyzed its expression in mammalian germ cells. The MLH3 gene is expressed in mouse meiotic cells and in human testis, and, as revealed by immunoprecipitation assays, the MLH3 protein is found in mouse spermatocytes. We further demonstrate that the meiosis-specific MSH4 protein, known to participate to meiotic recombination, is co-immunoprecipitated with MLH3 from mouse meiotic cell extracts. In addition, the two MLH3 protein isoforms potentially expressed in human testis (hMLH3 and hMLH3
7) interact in vitro with the hMSH4 protein. These interaction data suggest that MLH3 is associated with MSH4 in mammalian meiotic cells, and strongly support the possibility that MLH3 plays a role in mammalian meiotic recombination.
* To whom correspondence should be addressed. Tel: +33 493377724; Fax: +33 493533071; Email: paquis{at}hermes.unice.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. S. Johnston, W. W. Wright, P. DiCandeloro, E. Wilson, G. S. Kopf, and S. A. Jelinsky Stage-specific gene expression is a fundamental characteristic of rat spermatogenic cells and Sertoli cells PNAS, June 17, 2008; 105(24): 8315 - 8320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Nishant, A. J. Plys, and E. Alani A Mutation in the Putative MLH3 Endonuclease Domain Confers a Defect in Both Mismatch Repair and Meiosis in Saccharomyces cerevisiae Genetics, June 1, 2008; 179(2): 747 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Svetlanov, F. Baudat, P. E. Cohen, and B. de Massy Distinct Functions of MLH3 at Recombination Hot Spots in the Mouse Genetics, April 1, 2008; 178(4): 1937 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Lin, M. Nei, and H. Ma The origins and early evolution of DNA mismatch repair genes multiple horizontal gene transfers and co-evolution Nucleic Acids Res., December 3, 2007; 35(22): 7591 - 7603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Taylor, M. A. Powell, R. K. Gibb, J. S. Rader, P. C. Huettner, S. N. Thibodeau, D. G. Mutch, and P. J. Goodfellow MLH3 Mutation in Endometrial Cancer. Cancer Res., August 1, 2006; 66(15): 7502 - 7508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Cohen, S. E. Pollack, and J. W. Pollard Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals Endocr. Rev., June 1, 2006; 27(4): 398 - 426. [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. Oliver-Bonet, P.J. Turek, F. Sun, E. Ko, and R.H. Martin Temporal progression of recombination in human males Mol. Hum. Reprod., July 1, 2005; 11(7): 517 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Rana, N. D. Ebenezer, A. R. Webster, A. R. Linares, D. B. Whitehouse, S. Povey, and A. J. Hardcastle Recombination hotspots and block structure of linkage disequilibrium in the human genome exemplified by detailed analysis of PGM1 on 1p31 Hum. Mol. Genet., December 15, 2004; 13(24): 3089 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Neyton, F. Lespinasse, P. B. Moens, R. Paul, P. Gaudray, V. Paquis-Flucklinger, and S. Santucci-Darmanin Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis Mol. Hum. Reprod., December 1, 2004; 10(12): 917 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Hoffmann, P. V. Shcherbakova, T. A. Kunkel, and R. H. Borts MLH1 Mutations Differentially Affect Meiotic Functions in Saccharomyces cerevisiae Genetics, February 1, 2003; 163(2): 515 - 526. [Abstract] [Full Text] [PDF]
|
|