R152C DNA Pol ? mutation impairs base excision repair and induces cellular transformation.

ABSTRACT: DNA polymerase ? (Pol ?) is a key enzyme in DNA base excision repair (BER), a pathway that maintains genome integrity and stability. Pol ? mutations have been detected in various types of cancers, suggesting a possible linkage between Pol ? mutations and cancer. However, it is not clear whether and how Pol ? mutations cause cancer onset and progression. In the current work, we show that a substitution mutation, R152C, impairs Pol ? polymerase activity and BER efficiency. Cells harboring Pol ? R152C are sensitive to the DNA damaging agents methyl methanesulfonate (MMS) and H2O2. Moreover, the mutant cells display a high frequency of chromatid breakages and aneuploidy and also form foci. Taken together, our data indicate that Pol ? R152C can drive cellular transformation.

SUBMITTER: Zhou T 

PROVIDER: S-EPMC4872757 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature