MUTYH
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MUTYH (mutY Homolog (E. coli)) is a human gene that carries the instructions for cells to make an enzyme that is involved in the repair of DNA. This enzyme, MUTYH glycosylase, corrects particular mistakes that are made when DNA is copied (replicated) in preparation for cell division. The building blocks of DNA (base pairs) have specific partners. Normally, adenine pairs with thymine (written as A-T) and guanine pairs with cytosine (G-C). During the normal cellular activities, guanine sometimes becomes altered by oxygen, which causes it to pair with adenine instead of cytosine. MYH glycosylase fixes these mistakes so mutations don't accumulate in the DNA and lead to tumor formation and possibly cancer. This type of repair is known as base excision repair (BER).
The MUTYH gene is located on the short (p) arm of chromosome 1 between positions 34.3 and 32.1, from base pair 45,464,007 to base pair 45,475,152.
[edit] Related conditions
Mutations in the MUTYH gene cause an autosomal recessive form of familial adenomatous polyposis (also called MUTYH-associated polyposis). Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. Both copies of the MUTYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian Europeans are exchanges of amino acids (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine with cysteine at position 165 (also written as Tyr165Cys or Y165C). The other common mutation switches the amino acid glycine with aspartic acid at position 382 (also written as Gly382Asp or G382D).
[edit] References
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- Kambara T, Whitehall VL, Spring KJ, Barker MA, Arnold S, Wynter CV, Matsubara N, Tanaka N, Young JP, Leggett BA, Jass JR (2004). "Role of inherited defects of MYH in the development of sporadic colorectal cancer". Genes Chromosomes Cancer 40 (1): 1-9. PMID 15034862.
- Lipton L, Halford SE, Johnson V, Novelli MR, Jones A, Cummings C, Barclay E, Sieber O, Sadat A, Bisgaard ML, Hodgson SV, Aaltonen LA, Thomas HJ, Tomlinson IP (2003). "Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway". Cancer Res 63 (22): 7595-9. PMID 14633673.
- Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP (2003). "Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH". Lancet 362 (9377): 39-41. PMID 12853198.
- Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP (2003). "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH". N Engl J Med 348 (9): 791-9. PMID 12606733.
- Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN (2004). "High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis". Gastroenterology 126 (7): 1681-5. PMID 15188161.
- Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC, French AJ, Johnson RA, Burgart LJ, Rabe K, Lindor NM, Thibodeau SN (2004). "MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps". Gastroenterology 127 (1): 9-16. PMID 15236166.
