Home LiteratureArticle Details
PMID: 10809667 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice.

Genes & development ·Vol. 14 ·No. 9 ·2000-05-01 ·Pages 1085-97

Kneitz B, Cohen PE, Avdievich E, Zhu L, Kane MF, Hou H, Kolodner RD, Kucherlapati R, Pollard JW, Edelmann W

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.

MeSH Terms
Animals Base Pair Mismatch Cell Cycle Proteins Chromosome Mapping DNA Repair DNA-Binding Proteins/genetics Embryonic and Fetal Development Female Gene Expression Regulation, Developmental Infertility, Female/genetics Infertility, Male/genetics Male Meiosis/genetics Mice Mice, Knockout Proteins/genetics,metabolism Rad51 Recombinase
Chemicals
Cell Cycle Proteins DNA-Binding Proteins MSH4 protein, human Msh4 protein, mouse Proteins Rad51 Recombinase Rad51 protein, mouse
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kneitz B
Department of Cell Biology, Albert Einstein College of Medicine, The Bronx, New York 10461 USA.
Cohen P E
Avdievich E
Zhu L
Kane M F
Hou H
Kolodner R D
Kucherlapati R
Pollard J W
Edelmann W
References (50)
50 references, click to expand
  1. Crossing over during Caenorhabditis elegans meiosis requires a conserved MutS-based pathway that is partially dispensable in budding yeast.
    Genetics. 1999 Nov;153(3):1271-83 PMID: 10545458
  2. The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations.
    Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12404-9 PMID: 9770499
  3. Multiple functions of MutS- and MutL-related heterocomplexes.
    Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14186-8 PMID: 10588673
  4. MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability.
    Nat Genet. 2000 Jan;24(1):27-35 PMID: 10615123
  5. Mammalian DNA mismatch repair.
    Annu Rev Genet. 1999;33:533-64 PMID: 10690417
  6. The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression.
    Cancer Res. 2000 Feb 15;60(4):803-7 PMID: 10706084
  7. Chiasmata, meiotic univalents, and age in relation to aneuploid imbalance in mice.
    Cytogenet Cell Genet. 1976;16(6):505-29 PMID: 975936
  8. 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 Jun;163(2):331-40 PMID: 8200475
  9. Germ-line msh6 mutations in colorectal cancer families.
    Cancer Res. 1999 Oct 15;59(20):5068-74 PMID: 10537275
  10. HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions.
    Nat Genet. 1999 Nov;23(3):359-62 PMID: 10545954
  11. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast.
    Science. 1994 Aug 19;265(5175):1091-3 PMID: 8066446
  12. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction.
    Cell. 1994 Dec 16;79(6):1069-80 PMID: 8001134
  13. 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 Feb 15;9(4):455-70 PMID: 7533739
  14. 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 Mar 14;92(6):1950-4 PMID: 7892206
  15. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair.
    Genes Dev. 1995 Jul 15;9(14):1728-39 PMID: 7622037
  16. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis.
    Cell. 1995 Jul 28;82(2):309-19 PMID: 7628019
  17. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer.
    Cell. 1995 Jul 28;82(2):321-30 PMID: 7628020
  18. MSH2 deficient mice are viable and susceptible to lymphoid tumours.
    Nat Genet. 1995 Sep;11(1):64-70 PMID: 7550317
  19. Roles for two RecA homologs in promoting meiotic chromosome synapsis.
    Genes Dev. 1995 Nov 1;9(21):2684-95 PMID: 7590245
  20. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair.
    Genes Dev. 1996 Feb 15;10(4):407-20 PMID: 8600025
  21. Biochemistry and genetics of eukaryotic mismatch repair.
    Genes Dev. 1996 Jun 15;10(12):1433-42 PMID: 8666228
  22. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over.
    Nat Genet. 1996 Jul;13(3):336-42 PMID: 8673133
  23. Meiotic pachytene arrest in MLH1-deficient mice.
    Cell. 1996 Jun 28;85(7):1125-34 PMID: 8674118
  24. Mismatch repair in replication fidelity, genetic recombination, and cancer biology.
    Annu Rev Biochem. 1996;65:101-33 PMID: 8811176
  25. Lessons from hereditary colorectal cancer.
    Cell. 1996 Oct 18;87(2):159-70 PMID: 8861899
  26. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6.
    Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13629-34 PMID: 8942985
  27. Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis.
    Genes Dev. 1997 Jun 15;11(12):1573-82 PMID: 9203583
  28. Functional domains of the Saccharomyces cerevisiae Mlh1p and Pms1p DNA mismatch repair proteins and their relevance to human hereditary nonpolyposis colorectal cancer-associated mutations.
    Mol Cell Biol. 1997 Aug;17(8):4465-73 PMID: 9234704
  29. Cloning and expression analysis of a meiosis-specific MutS homolog: the human MSH4 gene.
    Genomics. 1997 Sep 1;44(2):188-94 PMID: 9299235
  30. Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer.
    Mol Cell Biol. 1998 Nov;18(11):6616-23 PMID: 9774676
  31. Cloning and characterization of the human and Caenorhabditis elegans homologs of the Saccharomyces cerevisiae MSH5 gene.
    Genomics. 1998 Oct 1;53(1):69-80 PMID: 9787078
  32. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis.
    Nat Genet. 1999 Jan;21(1):123-7 PMID: 9916805
  33. hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis.
    Cancer Res. 1999 Feb 15;59(4):816-22 PMID: 10029069
  34. Eukaryotic DNA mismatch repair.
    Curr Opin Genet Dev. 1999 Feb;9(1):89-96 PMID: 10072354
  35. Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis.
    Genes Dev. 1999 Mar 1;13(5):523-31 PMID: 10072381
  36. Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice.
    J Cell Biol. 1999 Jun 28;145(7):1395-406 PMID: 10385520
  37. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations.
    Am J Hum Genet. 1999 Nov;65(5):1291-8 PMID: 10521294
  38. Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer.
    Gastroenterology. 1997 Oct;113(4):1146-58 PMID: 9322509
  39. Meiotic chromosomes: it takes two to tango.
    Genes Dev. 1997 Oct 15;11(20):2600-21 PMID: 9334324
  40. Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex.
    Curr Biol. 1997 Oct 1;7(10):790-3 PMID: 9368761
  41. Conserved properties between functionally distinct MutS homologs in yeast.
    J Biol Chem. 1997 Nov 28;272(48):30345-9 PMID: 9374523
  42. Mutation in the mismatch repair gene Msh6 causes cancer susceptibility.
    Cell. 1997 Nov 14;91(4):467-77 PMID: 9390556
  43. Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair.
    Nat Genet. 1998 Mar;18(3):276-9 PMID: 9500552
  44. Functional overlap in mismatch repair by human MSH3 and MSH6.
    Genetics. 1998 Apr;148(4):1637-46 PMID: 9560383
  45. Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog.
    Mol Cell. 1998 Apr;1(5):697-705 PMID: 9660953
  46. The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis during meiosis.
    Mol Cell. 1998 Apr;1(5):707-18 PMID: 9660954
  47. Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha.
    J Biol Chem. 1998 Jul 31;273(31):19895-901 PMID: 9677427
  48. Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I.
    Development. 1998 Oct;125(20):4007-17 PMID: 9735362
  49. Cloning, structural characterization, and chromosomal localization of the human orthologue of Saccharomyces cerevisiae MSH5 gene.
    Genomics. 1998 Aug 15;52(1):50-61 PMID: 9740671
  50. Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13914-9 PMID: 10570173
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2000-05-01
Pages
1085-97
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316572
Subset
IM
Grants
NIGMS NIH HHS · GM26017 · United States
NCI NIH HHS · U01 CA084301 · United States
NIGMS NIH HHS · R37 GM026017 · United States
NCI NIH HHS · R01 CA076329 · United States
NCI NIH HHS · CA 76329 · United States
NIGMS NIH HHS · R01 GM026017 · United States
NCI NIH HHS · CA 84301 · United States
NCI NIH HHS · P30 CA013330 · United States
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2