Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer.
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.
Wooden
Steven H
SH
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX 77555-1071, USA.
Bassett
Heather M
HM
Wood
Thomas G
TG
McCullough
Amanda K
AK
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
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase