MutY and MutY homologs (MYH) in genome maintenance.
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.
Lu
A-Lien
AL
Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, Maryland 21201, USA. aluchang@umaryland.edu
Bai
Haibo
H
Shi
Guoli
G
Chang
Dau-Yin
DY
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
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase