title: Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis.
abstract: The MutY homolog (MYH) can excise adenines misincorporated opposite to guanines or 7,8-dihydro-8-oxo-guanines (8-oxoG) during DNA replication; thereby preventing G:C to T:A transversions. Germline mutations in the human MYH gene are associated with recessive inheritance of colorectal adenomatous polyposis (MAP). Here, we characterize one newly identified MAP-associated MYH missense mutation (R231L) that lies adjacent to the putative hMSH6 binding domain. The R231L mutant protein has severe defects in A/GO binding and in adenine glycosylase activities. The mutant fails to complement mutY-deficiency in Escherichia coli, but does not affect binding to hMSH6. These data support the role of the hMYH pathway in carcinogenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Haibo
authors.initials: H
authors.lastname: Bai
authors.forename: Scott
authors.initials: S
authors.lastname: Grist
authors.forename: Justin
authors.initials: J
authors.lastname: Gardner
authors.forename: Graeme
authors.initials: G
authors.lastname: Suthers
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Wilson
authors.forename: A-Lien
authors.initials: AL
authors.lastname: Lu
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011485:Protein Binding
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase