MSH2

MSH2And Its Role in Cancer

http://en.wikipedia.org/wiki/File:Protein_MSH2_PDB_2o8b.png

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

What is the Protein’s Normal Role in the Cell?

DNA mismatch repair (MMR)

oRemoving misincorporated nucleotides •base-base mismatches • insertion/deletion loops

oTrinucleotide repeat expansion (TRE)

Molecular Machinery

Protein’s Biological Role in the Organism

Wind, et al., 1995

Cranston, et al. 1997

Cranston, et al. 1997.

Msh2-/- and p53-/- male

Msh2-/- and p53-/- female

Wildtype female embryo

Msh2-/- and p53-/- female embryo

Protein’s Role in Cancer

• Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)

• Muir-Toree Syndrome

• Mismatch repair cancer syndrome

Lynch Syndrome (HNPCC)

http://www.myriadresourceguide.com/colaris/risk.htm

Treatment

http://www.polyposisregistry.org.uk/history/history2.htm

http://www.ccsb.org/Cancer/Summary/CDR0000062963/

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.