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MSH2

http:// en.wikipedia.org /wiki/File:Protein_MSH2_PDB_2o8b.png. MSH2. And Its Role in Cancer. About. mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli ) Tumor suppressor 2805 base pairs 16 exons Mutations are distributed evenly across gene

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MSH2

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  1. http://en.wikipedia.org/wiki/File:Protein_MSH2_PDB_2o8b.png MSH2 And Its Role in Cancer

  2. About mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) Tumor suppressor 2805 base pairs 16 exons Mutations are distributed evenly across gene Heterodimer with DNA binding and ADP binding http://ghr.nlm.nih.gov/gene/MSH2

  3. What is the Protein’s Normal Role in the Cell? DNA mismatch repair (MMR) • Removing misincorporated nucleotides • base-base mismatches • insertion/deletion loops • Trinucleotide repeat expansion (TRE)

  4. Molecular Machinery

  5. Protein’s Biological Role in the Organism Wind, et al., 1995 Cranston, et al. 1997

  6. Msh2-/- and p53-/- male Msh2-/- and p53-/- female Cranston, et al. 1997. Wildtype female embryo Msh2-/- and p53-/- female embryo

  7. Protein’s Role in Cancer • Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) • Muir-ToreeSyndrome • Mismatch repair cancer syndrome

  8. Lynch Syndrome (HNPCC) http://www.myriadresourceguide.com/colaris/risk.htm

  9. Treatment http://www.polyposisregistry.org.uk/history/history2.htm http://www.ccsb.org/Cancer/Summary/CDR0000062963/

  10. References • http://ghr.nlm.nih.gov/gene/MSH2 • http://ghr.nlm.nih.gov/condition/lynch-syndrome • http://omim.org/entry/609309 • http://omim.org/entry/120435 • http://genefacts.org/index.php?option=com_content&view=article&id=492:management&catid=113:lynch-syndrome&Itemid=665 • http://www.myriadresourceguide.com/colaris/genes.htm • Peña-Diaz, Javier. Mammalian mismatch repair: error-free or error-prone?Trends in Biochemical Sciences. May 2012 Vol. 37, No. 5 • Wind, Niels et al. Inactivation of the Mouse Msh2 Gene Results in Mismatch Repair Deficiency, Methylation Tolerance, Hyperrecombination, and Predisposition to Cancer. Cell. July 1995 Vol. 82, 321-330. • Cranston et al. Female embryonic lethality in mice nullizygous for both Msh2 and p53. Nature. 1997.

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