MutS Homolog 4 Localization to Meiotic Chromosomes is Required for Chromosome Pairing During Meiosis in Male and Female Mice

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2000 May 16

PMID 10809667

Citations 197

Authors

B Kneitz

P E Cohen

E Avdievich

L Zhu

M F Kane

H Hou Jr

R D Kolodner

R Kucherlapati

J W Pollard

W Edelmann

Affiliations

Soon will be listed here.

Abstract

Msh4 (MutS homolog 4) is a member of the mammalian mismatch repair gene family whose members are involved in postreplicative DNA mismatch repair as well as in the control of meiotic recombination. In this report we show that MSH4 has an essential role in the control of male and female meiosis. We demonstrate that MSH4 is present in the nuclei of spermatocytes early in prophase I and that it forms discrete foci along meiotic chromosomes during the zygotene and pachytene stages of meiosis. Disruption of the Msh4 gene in mice results in male and female sterility due to meiotic failure. Although meiosis is initiated in Msh4 mutant male and female mice, as indicated by the chromosomal localization of RAD51 and COR1 during leptonema/zygonema, the chromosomes fail to undergo normal pairing. Our results show that MSH4 localization on chromosomes during the early stages of meiosis is essential for normal chromosome synapsis in prophase I and that it acts in the same pathway as MSH5.

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References

Zalevsky J, MacQueen A, Duffy J, Kemphues K, Villeneuve A . Crossing over during Caenorhabditis elegans meiosis requires a conserved MutS-based pathway that is partially dispensable in budding yeast. Genetics. 1999; 153(3):1271-83. PMC: 1460811. DOI: 10.1093/genetics/153.3.1271. View

Flores-Rozas H, Kolodner R . The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Proc Natl Acad Sci U S A. 1998; 95(21):12404-9. PMC: 22844. DOI: 10.1073/pnas.95.21.12404. View

Nakagawa T, Datta A, Kolodner R . Multiple functions of MutS- and MutL-related heterocomplexes. Proc Natl Acad Sci U S A. 1999; 96(25):14186-8. PMC: 33940. DOI: 10.1073/pnas.96.25.14186. View

Lipkin S, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis A, Lynch H . MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet. 1999; 24(1):27-35. DOI: 10.1038/71643. View

Buermeyer A, Deschenes S, Baker S, Liskay R . Mammalian DNA mismatch repair. Annu Rev Genet. 2000; 33:533-64. DOI: 10.1146/annurev.genet.33.1.533. View

Edelmann W, Umar A, Yang K, HEYER J, Kucherlapati M, Lia M . The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Res. 2000; 60(4):803-7. View

POLANI P, JAGIELLO G . Chiasmata, meiotic univalents, and age in relation to aneuploid imbalance in mice. Cytogenet Cell Genet. 1976; 16(6):505-29. DOI: 10.1159/000130668. View

Enders G, May 2nd J . Developmentally regulated expression of a mouse germ cell nuclear antigen examined from embryonic day 11 to adult in male and female mice. Dev Biol. 1994; 163(2):331-40. DOI: 10.1006/dbio.1994.1152. View

Kolodner R, Tytell J, Schmeits J, Kane M, Gupta R, Weger J . Germ-line msh6 mutations in colorectal cancer families. Cancer Res. 1999; 59(20):5068-74. View

10.

de Wind N, Dekker M, Claij N, Jansen L, van Klink Y, Radman M . HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. Nat Genet. 1999; 23(3):359-62. DOI: 10.1038/15544. View

11.

Prolla T, Pang Q, Alani E, Kolodner R, Liskay R . MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994; 265(5175):1091-3. DOI: 10.1126/science.8066446. View

12.

Ross-Macdonald P, Roeder G . Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell. 1994; 79(6):1069-80. DOI: 10.1016/0092-8674(94)90037-x. View

13.

Bedell M, Brannan C, Evans E, Copeland N, Jenkins N, Donovan P . DNA rearrangements located over 100 kb 5' of the Steel (Sl)-coding region in Steel-panda and Steel-contrasted mice deregulate Sl expression and cause female sterility by disrupting ovarian follicle development. Genes Dev. 1995; 9(4):455-70. DOI: 10.1101/gad.9.4.455. View

14.

Li G, Modrich P . Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs. Proc Natl Acad Sci U S A. 1995; 92(6):1950-4. PMC: 42400. DOI: 10.1073/pnas.92.6.1950. View

15.

Hollingsworth N, Ponte L, Halsey C . MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev. 1995; 9(14):1728-39. DOI: 10.1101/gad.9.14.1728. View

16.

Baker S, Bronner C, Zhang L, Plug A, Robatzek M, Warren G . Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995; 82(2):309-19. DOI: 10.1016/0092-8674(95)90318-6. View

17.

de Wind N, Dekker M, Berns A, Radman M, Te Riele H . Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995; 82(2):321-30. DOI: 10.1016/0092-8674(95)90319-4. View

18.

Reitmair A, Schmits R, Ewel A, Bapat B, Redston M, Mitri A . MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet. 1995; 11(1):64-70. DOI: 10.1038/ng0995-64. View

19.

Rockmill B, Sym M, Scherthan H, Roeder G . Roles for two RecA homologs in promoting meiotic chromosome synapsis. Genes Dev. 1995; 9(21):2684-95. DOI: 10.1101/gad.9.21.2684. View

20.

Marsischky G, Filosi N, Kane M, Kolodner R . Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev. 1996; 10(4):407-20. DOI: 10.1101/gad.10.4.407. View