title: Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer.
abstract: Mutations found in human tumors often include transversions of GC to TA that may result from the mis-pairing of 8-oxoG with adenine during DNA replication. The human MutY (hMYH) enzyme, an adenine-specific DNA glycosylase, initiates repair at this mismatch. It has recently been demonstrated that inherited variants of hMYH may predispose individuals to multiple colorectal adenomas and carcinoma [Nat. Genet. 30 (2002) 227]. In this study, we demonstrate that two of these cancer-associated hMYH mutants, Y165C and G382D, are devoid of glycosylase activity directed towards 8-oxoG:A mispairs. These findings implicate a total loss of hMYH function associated with colorectal cancers.
authors.affiliation: Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX 77555-1071, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Wooden
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bassett
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wood
authors.forename: Amanda K
authors.initials: AK
authors.lastname: McCullough
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch; D015153:Blotting, Western; D002999:Clone Cells; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D016297:Mutagenesis, Site-Directed; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase