MLH1

MutL homolog 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsMLH1 ; COCA2; FCC2; HNPCC; HNPCC2; hMLH1
External IDsOMIM: 120436 MGI: 101938 HomoloGene: 208 GeneCards: MLH1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez429217350
EnsemblENSG00000076242ENSMUSG00000032498
UniProtP40692Q9JK91
RefSeq (mRNA)NM_000249NM_026810
RefSeq (protein)NP_000240NP_081086
Location (UCSC)Chr 3:
37.03 – 37.11 Mb		Chr 9:
111.23 – 111.27 Mb
PubMed search

MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli), also known as mlh1, is a human gene located on Chromosome 3. It is a gene commonly associated with hereditary nonpolyposis colorectal cancer.

Function

This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). It is a human homolog of the E. coli DNA mismatch repair gene, mutL, which mediates protein-protein interactions during mismatch recognition, strand discrimination, and strand removal. Defects in MLH1 are associated with the microsatellite instability (MSI) observed in HNPCC. Alternatively spliced transcript variants encoding different isoforms have been described, but their full-length natures have not been determined.[1]

Clinical significance

It can also be associated with Turcot syndrome.[2]

Interactions

MLH1 has been shown to interact with:

See also

References

  1. ↑ "Entrez Gene: MLH1 mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)".
  2. ↑ Lebrun C, Olschwang S, Jeannin S, Vandenbos F, Sobol H, Frenay M (2007). "Turcot syndrome confirmed with molecular analysis". Eur. J. Neurol. 14 (4): 470–2. doi:10.1111/j.1468-1331.2006.01669.x. PMID 17389002.
  3. ↑ Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. PMC 316544. PMID 10783165.
  4. ↑ Langland G, Kordich J, Creaney J, Goss KH, Lillard-Wetherell K, Bebenek K et al. (August 2001). "The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair". J. Biol. Chem. 276 (32): 30031–5. doi:10.1074/jbc.M009664200. PMID 11325959.
  5. ↑ Freire R, d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson ID et al. (August 2001). "Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIalpha". Nucleic Acids Res. 29 (15): 3172–80. doi:10.1093/nar/29.15.3172. PMC 55826. PMID 11470874.
  6. ↑ Pedrazzi G, Perrera C, Blaser H, Kuster P, Marra G, Davies SL et al. (November 2001). "Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1". Nucleic Acids Res. 29 (21): 4378–86. doi:10.1093/nar/29.21.4378. PMC 60193. PMID 11691925.
  7. ↑ Schmutte C, Sadoff MM, Shim KS, Acharya S, Fishel R (August 2001). "The interaction of DNA mismatch repair proteins with human exonuclease I". J. Biol. Chem. 276 (35): 33011–8. doi:10.1074/jbc.M102670200. PMID 11427529.
  8. ↑ Bellacosa A, Cicchillitti L, Schepis F, Riccio A, Yeung AT, Matsumoto Y et al. (March 1999). "MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1". Proc. Natl. Acad. Sci. U.S.A. 96 (7): 3969–74. doi:10.1073/pnas.96.7.3969. PMC 22404. PMID 10097147.
  9. ↑ Santucci-Darmanin S, Walpita D, Lespinasse F, Desnuelle C, Ashley T, Paquis-Flucklinger V (August 2000). "MSH4 acts in conjunction with MLH1 during mammalian meiosis". FASEB J. 14 (11): 1539–47. doi:10.1096/fj.14.11.1539. PMID 10928988.
  10. ↑ 10.0 10.1 Mac Partlin M, Homer E, Robinson H, McCormick CJ, Crouch DH, Durant ST et al. (February 2003). "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene 22 (6): 819–25. doi:10.1038/sj.onc.1206252. PMID 12584560.
  11. ↑ Kondo E, Horii A, Fukushige S (April 2001). "The interacting domains of three MutL heterodimers in man: hMLH1 interacts with 36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2". Nucleic Acids Res. 29 (8): 1695–702. doi:10.1093/nar/29.8.1695. PMC 31313. PMID 11292842.
  12. ↑ Guerrette S, Acharya S, Fishel R (March 1999). "The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer". J. Biol. Chem. 274 (10): 6336–41. doi:10.1074/jbc.274.10.6336. PMID 10037723.

Further reading

  • Paraf F, Sasseville D, Watters AK, Narod S, Ginsburg O, Shibata H et al. (1995). "Clinicopathological relevance of the association between gastrointestinal and sebaceous neoplasms: the Muir-Torre syndrome.". Hum. Pathol. 26 (4): 422–7. doi:10.1016/0046-8177(95)90144-2. PMID 7705822.
  • Kolodner RD (1996). "Mismatch repair: mechanisms and relationship to cancer susceptibility.". Trends Biochem. Sci. 20 (10): 397–401. doi:10.1016/S0968-0004(00)89087-8. PMID 8533151.
  • Peltomäki P, de la Chapelle A (1997). "Mutations predisposing to hereditary nonpolyposis colorectal cancer.". Adv. Cancer Res. 71: 93–119. doi:10.1016/S0065-230X(08)60097-4. PMID 9111864.
  • Papadopoulos N, Lindblom A (1997). "Molecular basis of HNPCC: mutations of MMR genes.". Hum. Mutat. 10 (2): 89–99. doi:10.1002/(SICI)1098-1004(1997)10:2<89::AID-HUMU1>3.0.CO;2-H. PMID 9259192.
  • Kauh J, Umbreit J (2004). "Colorectal cancer prevention.". Current Problems in Cancer 28 (5): 240–64. doi:10.1016/j.currproblcancer.2004.05.004. PMID 15375803.
  • Warusavitarne J, Schnitzler M (2007). "The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer.". International journal of colorectal disease 22 (7): 739–48. doi:10.1007/s00384-006-0228-0. PMID 17109103.
  • Niv Y (2007). "Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer.". World J. Gastroenterol. 13 (12): 1767–9. PMID 17465465.

External links