(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
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.
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
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).
- Cheadle JP, Sampson JR (2003). "Exposing the MYtH about base excision repair and human inherited disease". Hum Mol Genet 12 Spec No 2 R159–65.
- Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S (2004). "Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk". J Natl Cancer Inst 96 (21): 1631–4.
- Fleischmann C, Peto J, Cheadle J, Shah B, Sampson J, Houlston RS (2004). "Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer". Int J Cancer 109 (4): 554–8.
- Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP (2002). "Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations". Hum Mol Genet 11 (23): 2961–7.
- Jones S, Lambert S, Williams GT, Best JM, Sampson JR, Cheadle JP (2004). "Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas". Br J Cancer 90 (8): 1591–3.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.