Understanding the loss-of-function in a triple missense mutant of DNA polymerase β found in prostate cancer.

ABSTRACT: Human DNA polymerase (pol) β is essential for base excision repair. We previously reported a triple somatic mutant of pol β (p.P261L/T292A/I298T) found in an early onset prostate tumor. This mutation abolishes polymerase activity, and the wild-type allele was not present in the tumor, indicating a complete deficiency in pol β function. The effect on polymerase activity is unexpected because the point mutations that comprise the triple mutant are not part of the active site. Herein, we demonstrate the mechanism of this loss-of-function. In order to understand the effect of the individual point mutations we biochemically analyzed all single and double mutants that comprise the triple mutant. We found that the p.I298T mutation is responsible for a marked instability of the triple mutant prote

SUBMITTER: An C 

PROVIDER: S-EPMC3981039 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature