Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis.
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.
Bai
Haibo
H
Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD 21201, USA.
Grist
Scott
S
Gardner
Justin
J
Suthers
Graeme
G
Wilson
Teresa M
TM
Lu
A-Lien
AL
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
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase