The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MSH4  -  mutS homolog 4

Homo sapiens

Synonyms: MutS protein homolog 4, hMSH4
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of MSH4

  • To date, the implication of MSH4 mutations has not been established in human sterility [1].

High impact information on MSH4

  • 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 [2].
  • 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 [2].
  • Here, we demonstrate that purified hMSH4-hMSH5 binds uniquely to Holliday Junctions [3].
  • The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination [4].
  • As a step forward to the understanding of the molecular mechanisms underlying the roles of these two mammalian MutS homologues, here we have identified von Hippel-Lindau (VHL) tumor suppressor-binding protein 1 (VBP1) as an interacting protein partner for human MSH4 (hMSH4) [5].

Biological context of MSH4

  • Immunolocalization analysis shows that MSH4 is present at sites along the synaptonemal complex as soon as homologous chromosomes synapse [6].
  • These results suggest that MSH4 is first required for chromosome synapsis and that this MutS homologue is involved later with MLH1 in meiotic reciprocal recombination [6].
  • MSH4 acts in conjunction with MLH1 during mammalian meiosis [6].
  • The number of MSH4 foci decreases gradually as pachynema progresses [6].
  • As a step towards understanding the molecular mechanisms underlying the role of MSH4 in human gametogenesis, we decided to determine whether this protein interacts with recombination machinery enzymes [1].

Anatomical context of MSH4

  • By Northern blot analysis, human MSH4 transcripts are only detectable in testis and in ovary with a lower level of expression [7].

Associations of MSH4 with chemical compounds


Physical interactions of MSH4


Co-localisations of MSH4

  • During this transition, MLH1 foci begin to appear and colocalize with MSH4 [6].

Other interactions of MSH4

  • Mammalian MSH4 and MSH5 proteins form a heterodimeric complex and play an important role in the meiotic processes [5].
  • 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 [4].
  • Immunolocalization analyses show that some MSH4 foci, located on mouse meiotic chromosomes, colocalize with DMC1/RAD51 complexes [1].
  • Formation of hMSH4-hMSH5 heterocomplex is a prerequisite for subsequent GPS2 recruitment [9].

Analytical, diagnostic and therapeutic context of MSH4


  1. Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis. Neyton, S., Lespinasse, F., Moens, P.B., Paul, R., Gaudray, P., Paquis-Flucklinger, V., Santucci-Darmanin, S. Mol. Hum. Reprod. (2004) [Pubmed]
  2. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Kneitz, B., Cohen, P.E., Avdievich, E., Zhu, L., Kane, M.F., Hou, H., Kolodner, R.D., Kucherlapati, R., Pollard, J.W., Edelmann, W. Genes Dev. (2000) [Pubmed]
  3. hMSH4-hMSH5 recognizes Holliday Junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes. Snowden, T., Acharya, S., Butz, C., Berardini, M., Fishel, R. Mol. Cell (2004) [Pubmed]
  4. The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination. Santucci-Darmanin, S., Neyton, S., Lespinasse, F., Saunières, A., Gaudray, P., Paquis-Flucklinger, V. Hum. Mol. Genet. (2002) [Pubmed]
  5. Human MutS homologue MSH4 physically interacts with von Hippel-Lindau tumor suppressor-binding protein 1. Her, C., Wu, X., Griswold, M.D., Zhou, F. Cancer Res. (2003) [Pubmed]
  6. MSH4 acts in conjunction with MLH1 during mammalian meiosis. Santucci-Darmanin, S., Walpita, D., Lespinasse, F., Desnuelle, C., Ashley, T., Paquis-Flucklinger, V. FASEB J. (2000) [Pubmed]
  7. Cloning and expression analysis of a meiosis-specific MutS homolog: the human MSH4 gene. Paquis-Flucklinger, V., Santucci-Darmanin, S., Paul, R., Saunières, A., Turc-Carel, C., Desnuelle, C. Genomics (1997) [Pubmed]
  8. Physical and functional interaction between hMSH5 and c-Abl. Yi, W., Lee, T.H., Tompkins, J.D., Zhu, F., Wu, X., Her, C. Cancer Res. (2006) [Pubmed]
  9. Formation of hMSH4-hMSH5 heterocomplex is a prerequisite for subsequent GPS2 recruitment. Lee, T.H., Yi, W., Griswold, M.D., Zhu, F., Her, C. DNA Repair (Amst.) (2006) [Pubmed]
WikiGenes - Universities