Abrir o menú principal
MSH4
Identificadores
Símbolo MSH4
Entrez 4438
UniProt O15457
Outros datos
Locus Cr. 1 :(75.8 – 75.91 Mb)

A proteína MSH4 ou proteína MutS homólogo 4 é unha proteína que en humanos está codificada no xene MSH4 do cromosoma 1.[1][2]

FunciónEditar

As proteínas MSH4 e MSH5 forman unha estrutura heterooligomérica (heterodímero) en lévedos e humanos.[3][4][5] No lévedo Saccharomyces cerevisiae MSH4 e MSH5 actúan especificamente para facilitar sobrecruzamentos entre cromosomas homólogos durante a meiose.[3] O complexo MSH4/MSH5 únese a unións de Holliday dobres e estabilízaas, e promociona a súa resolución en produtos de sobrecruzamento. Un mutante hipomórfico (parcialmente funcional) de MSH4 en S. cerevisiae mostrou un 30% de redución en todo o xenoma no número de sobrecruzamentos, e un gran número de meioses sen intercambio de cromosomas.[6] Non obstante, este mutante dá lugar a patróns de viabilidade de esporas que suxiren que a segregación de cromosomas sen intercambio ocorría eficazmente. Así, en S. cerevisiae, unha segregación cromosómica correcta aparentemente non depende enteiramente dos sobrecruzamentos cos seus pares homólogos.

O xene him-14 do verme Caenorhabditis elegans codifica un ortólogo de MSH4.[7] A formación de sobrecruzamentos durante a meiose de C. elegans require o xene him-14(MSH4). A perda da función de him-14(MSH-4) reduce drasticamente o sobrecruzamento, o que ten como resultado a falta de quiasmas entre os homólogos e unha segregación anormal. Así, en C. elegans, a segregación aparentemente depende dos sobrecruzamentos entre os pares homologos. O xene him-14(MSH4) funciona durante a fase de paquiteno da meiose, o que indica que non é necesario para estabilizar as fases precedentes de apareamento e sinapse dos cromosomas homólogos.

Nun mutante para MSH4 do arroz, a frecuencia de quiasmas decrecía drasticamente nun 10% con respecto á frecuencia do tipo salvaxe, aínda que o complexo sinaptonémico se instalaba normalmente.[8] É probable que a MSH4 interaccione con MSH5 para promover a maioría dos sobrecruzamentos durante a meiose do arroz.

En xeral parece que MSH4 actúa durante a meiose para dirixir a reparación recombinacional dalgunhas roturas de dobre febra do ADN cara á opción do sobrecruzamento en vez de cara á opción de non sobrecruzamento (ver recombinación homóloga).

InteracciónsEditar

NotasEditar

  1. Paquis-Flucklinger V, Santucci-Darmanin S, Paul R, Saunières A, Turc-Carel C, Desnuelle C (Sep 1997). "Cloning and expression analysis of a meiosis-specific MutS homolog: the human MSH4 gene". Genomics 44 (2): 188–94. PMID 9299235. doi:10.1006/geno.1997.4857. 
  2. "Entrez Gene: MSH4 mutS homolog 4 (E. coli)". 
  3. 3,0 3,1 Pochart P, Woltering D, Hollingsworth NM (1997). "Conserved properties between functionally distinct MutS homologs in yeast". J. Biol. Chem. 272 (48): 30345–9. PMID 9374523. doi:10.1074/jbc.272.48.30345. 
  4. 4,0 4,1 Winand NJ, Panzer JA, Kolodner RD (1998). "Cloning and characterization of the human and Caenorhabditis elegans homologs of the Saccharomyces cerevisiae MSH5 gene". Genomics 53 (1): 69–80. PMID 9787078. doi:10.1006/geno.1998.5447. 
  5. 5,0 5,1 Bocker T, Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce CM, Copeland T, Kovatich AJ, Fishel R (1999). "hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis". Cancer Res. 59 (4): 816–22. PMID 10029069. 
  6. Krishnaprasad GN, Anand MT, Lin G, Tekkedil MM, Steinmetz LM, Nishant KT (2015). "Variation in crossover frequencies perturb crossover assurance without affecting meiotic chromosome segregation in Saccharomyces cerevisiae". Genetics 199 (2): 399–412. PMC 4317650. PMID 25467183. doi:10.1534/genetics.114.172320. 
  7. Zalevsky J, MacQueen AJ, Duffy JB, Kemphues KJ, Villeneuve AM (1999). "Crossing over during Caenorhabditis elegans meiosis requires a conserved MutS-based pathway that is partially dispensable in budding yeast". Genetics 153 (3): 1271–83. PMC 1460811. PMID 10545458. 
  8. Zhang L, Tang D, Luo Q, Chen X, Wang H, Li Y, Cheng Z (2014). "Crossover formation during rice meiosis relies on interaction of OsMSH4 and OsMSH5". Genetics 198 (4): 1447–56. PMID 25278554. doi:10.1534/genetics.114.168732. 
  9. Santucci-Darmanin S, Walpita D, Lespinasse F, Desnuelle C, Ashley T, Paquis-Flucklinger V (Aug 2000). "MSH4 acts in conjunction with MLH1 during mammalian meiosis". FASEB Journal 14 (11): 1539–47. PMID 10928988. doi:10.1096/fj.14.11.1539. 
  10. Her C, Wu X, Griswold MD, Zhou F (Feb 2003). "Human MutS homologue MSH4 physically interacts with von Hippel-Lindau tumor suppressor-binding protein 1". Cancer Research 63 (4): 865–72. PMID 12591739. 
  11. Santucci-Darmanin S, Neyton S, Lespinasse F, Saunières A, Gaudray P, Paquis-Flucklinger V (Jul 2002). "The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination". Human Molecular Genetics 11 (15): 1697–706. PMID 12095912. doi:10.1093/hmg/11.15.1697. 

Véxase taménEditar

BibliografíaEditar

  • Her C, Zhao N, Wu X, Tompkins JD (2007). "MutS homologues hMSH4 and hMSH5: diverse functional implications in humans". Frontiers in Bioscience 12: 905–11. PMID 17127347. doi:10.2741/2112. 
  • Winand NJ, Panzer JA, Kolodner RD (Oct 1998). "Cloning and characterization of the human and Caenorhabditis elegans homologs of the Saccharomyces cerevisiae MSH5 gene". Genomics 53 (1): 69–80. PMID 9787078. doi:10.1006/geno.1998.5447. 
  • Bocker T, Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce CM, Copeland T, Kovatich AJ, Fishel R (Feb 1999). "hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis". Cancer Research 59 (4): 816–22. PMID 10029069. 
  • Kneitz B, Cohen PE, Avdievich E, Zhu L, Kane MF, Hou H, Kolodner RD, Kucherlapati R, Pollard JW, Edelmann W (May 2000). "MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice". Genes & Development 14 (9): 1085–97. PMC 316572. PMID 10809667. 
  • Santucci-Darmanin S, Walpita D, Lespinasse F, Desnuelle C, Ashley T, Paquis-Flucklinger V (Aug 2000). "MSH4 acts in conjunction with MLH1 during mammalian meiosis". FASEB Journal 14 (11): 1539–47. PMID 10928988. doi:10.1096/fj.14.11.1539. 
  • Räschle M, Dufner P, Marra G, Jiricny J (Jun 2002). "Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSalpha". The Journal of Biological Chemistry 277 (24): 21810–20. PMID 11948175. doi:10.1074/jbc.M108787200. 
  • Moens PB, Kolas NK, Tarsounas M, Marcon E, Cohen PE, Spyropoulos B (Apr 2002). "The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA-DNA interactions without reciprocal recombination". Journal of Cell Science 115 (Pt 8): 1611–22. PMID 11950880. 
  • Santucci-Darmanin S, Neyton S, Lespinasse F, Saunières A, Gaudray P, Paquis-Flucklinger V (Jul 2002). "The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination". Human Molecular Genetics 11 (15): 1697–706. PMID 12095912. doi:10.1093/hmg/11.15.1697. 
  • Her C, Wu X, Griswold MD, Zhou F (Feb 2003). "Human MutS homologue MSH4 physically interacts with von Hippel-Lindau tumor suppressor-binding protein 1". Cancer Research 63 (4): 865–72. PMID 12591739. 
  • Snowden T, Acharya S, Butz C, Berardini M, Fishel R (Aug 2004). "hMSH4-hMSH5 recognizes Holliday Junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes". Molecular Cell 15 (3): 437–51. PMID 15304223. doi:10.1016/j.molcel.2004.06.040. 
  • Yi W, Wu X, Lee TH, Doggett NA, Her C (Jul 2005). "Two variants of MutS homolog hMSH5: prevalence in humans and effects on protein interaction". Biochemical and Biophysical Research Communications 332 (2): 524–32. PMID 15907804. doi:10.1016/j.bbrc.2005.04.154. 
  • Lee TH, Yi W, Griswold MD, Zhu F, Her C (Jan 2006). "Formation of hMSH4-hMSH5 heterocomplex is a prerequisite for subsequent GPS2 recruitment". DNA Repair 5 (1): 32–42. PMID 16122992. doi:10.1016/j.dnarep.2005.07.004. 
  • Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. PMID 16189514. doi:10.1038/nature04209. 
  • Neyton S, Lespinasse F, Lahaye F, Staccini P, Paquis-Flucklinger V, Santucci-Darmanin S (Oct 2007). "CRM1-dependent nuclear export and dimerization with hMSH5 contribute to the regulation of hMSH4 subcellular localization". Experimental Cell Research 313 (17): 3680–93. PMID 17869244. doi:10.1016/j.yexcr.2007.08.010. 

Ligazóns externasEditar