title: MutY and MutY homologs (MYH) in genome maintenance.
abstract: The base excision repair carried out by bacterial MutY DNA glycosylase and eukaryotic MutY homolog (MYH) is responsible for removing adenines misincorporated into DNA opposite G and 7,8-dihydro-8-oxo-guanines (8-oxoG); thereby preventing G:C to T:A mutations. Escherichia coli MutY (EcMutY) can also remove adenines from A/C and A/5-hydroxyuracil and can remove guanines from G/8-oxoG mismatches at reduced rates. Thus, MutY has a minor role in reducing the mutagenic effects on G:C to A:T transitions and G:C to C:G transversions. The eukaryotic MYH can excise adenines misincorporated opposite GO, G, or C; remove 2-hydroxyadenines mispaired with A,G, and GO; excise G from G/GO mismatch weakly, thereby preventing G:C to T:A transversions. The in vitro and in vivo activities of MYH can be modulated by several proteins including apurinic/apyrimidinic endonuclease (APE1), proliferating cell nuclear antigen (PCNA), and mismatch recognition enzymes MSH2/MSH6. Recently, MYH has been shown to associate with the checkpoint proteins, Rad9, Rad1, and Hus1 (referred as the 9-1-1 complex). Thus, MYH-mediated base excision repair is coordinated with mismatch repair, DNA replication, cell-cycle progression, and DNA-damage checkpoints. Biallelic germ-line mutations in the human MYH gene are associated with recessive inheritance of multiple colorectal adenomas and carcinoma. MYH mutations can cause G:C to T:A mutations of the adenomatous polyposis coli (APC), K-ras, and other genes that control cellular proliferation in the colon.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, Maryland 21201, USA. aluchang@umaryland.edu
authors.forename: A-Lien
authors.initials: AL
authors.lastname: Lu
authors.forename: Haibo
authors.initials: H
authors.lastname: Bai
authors.forename: Guoli
authors.initials: G
authors.lastname: Shi
authors.forename: Dau-Yin
authors.initials: DY
authors.lastname: Chang
mesh_terms: D000818:Animals; D002417:Cattle; D015179:Colorectal Neoplasms / Q000235:genetics; D045647:DNA Glycosylases / Q000172:deficiency / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D018816:Genes, cdc; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D013379:Substrate Specificity; D015003:Yeasts / Q000235:genetics
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase