MLH1

From Wikipedia, the free encyclopedia
MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
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
This box:

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.

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, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Alternatively spliced transcript variants encoding different isoforms have been described, but their full-length natures have not been determined.[1]

It can also be associated with Turcot syndrome.

Interactions

MLH1 has been shown to interact with Exonuclease 1,[2] MSH4,[3] PMS2,[4][5][6] Myc,[4] Bloom syndrome protein[7][8][9][10] and MBD4.[11]

See also

  • Mismatch_repair#MutH

References

  1. ↑ "Entrez Gene: MLH1 mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)". 
  2. ↑ Schmutte, C; Sadoff M M, Shim K S, Acharya S, Fishel R (August 2001). "The interaction of DNA mismatch repair proteins with human exonuclease I". J. Biol. Chem. (United States) 276 (35): 33011–8. doi:10.1074/jbc.M102670200. ISSN 0021-9258. PMID 11427529. 
  3. ↑ 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. (UNITED STATES) 14 (11): 1539–47. doi:10.1096/fj.14.11.1539. ISSN 0892-6638. PMID 10928988. 
  4. ↑ 4.0 4.1 Mac Partlin, Mary; Homer Elizabeth, Robinson Helen, McCormick Carol J, Crouch Dorothy H, Durant Stephen T, Matheson Elizabeth C, Hall Andrew G, Gillespie David A F, Brown Robert (February 2003). "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene (England) 22 (6): 819–25. doi:10.1038/sj.onc.1206252. ISSN 0950-9232. PMID 12584560. 
  5. ↑ 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. (England) 29 (8): 1695–702. doi:10.1093/nar/29.8.1695. PMC 31313. PMID 11292842. 
  6. ↑ Guerrette, S; Acharya S, Fishel R (March 1999). "The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer". J. Biol. Chem. (UNITED STATES) 274 (10): 6336–41. doi:10.1074/jbc.274.10.6336. ISSN 0021-9258. PMID 10037723. 
  7. ↑ Wang, Y; Cortez D, Yazdi P, Neff N, Elledge S J, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. (UNITED STATES) 14 (8): 927–39. ISSN 0890-9369. PMC 316544. PMID 10783165. 
  8. ↑ Langland, G; Kordich J, Creaney J, Goss K H, Lillard-Wetherell K, Bebenek K, Kunkel T A, Groden J (August 2001). "The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair". J. Biol. Chem. (United States) 276 (32): 30031–5. doi:10.1074/jbc.M009664200. ISSN 0021-9258. PMID 11325959. 
  9. ↑ Freire, R; d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson I D, Jackson S P (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. (England) 29 (15): 3172–80. doi:10.1093/nar/29.15.3172. PMC 55826. PMID 11470874. 
  10. ↑ Pedrazzi, G; Perrera C, Blaser H, Kuster P, Marra G, Davies S L, Ryu G H, Freire R, Hickson I D, Jiricny J, Stagljar I (November 2001). "Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1". Nucleic Acids Res. (England) 29 (21): 4378–86. doi:10.1093/nar/29.21.4378. PMC 60193. PMID 11691925. 
  11. ↑ Bellacosa, A; Cicchillitti L, Schepis F, Riccio A, Yeung A T, Matsumoto Y, Golemis E A, Genuardi M, Neri G (March 1999). "MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (7): 3969–74. doi:10.1073/pnas.96.7.3969. ISSN 0027-8424. PMC 22404. PMID 10097147. 

Further reading

  • Paraf F, Sasseville D, Watters AK, 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

Excision repair
Other forms of repair
Other/ungrouped proteins
Regulation
Other/ungrouped
See also: DNA repair-deficiency disorder B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)


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