Tumor ‐associated APE1 variant exhibits reduced complementation efficiency but does not promote cancer cell phenotypes

We report herein that the tumor‐associated APE1 variant, R237C, shows reduced complementation efficiency of the methyl methanesulfonate hypersensitivity and impaired cell growth exhibited by APE1‐deficient mouse embryonic fibroblasts. Overexpression of wild‐type APE1 or the R237C variant in the nontransformed C127I mouse cell line had no effect on proliferation, cell cycle status, steady‐state DNA damage levels, mitochondrial function, or cellular transformation. A human cell line heterozygous for an APE1 knockout allele had lower levels of endogenous APE1, increased cellular sensitivity to DNA‐damaging agents, impaired proliferation with time, and a distinct global gene expression pattern consistent with a stress phenotype. Our results indicate that: (i) the tumor‐associated R237C variant is a possible susceptibility factor, but not likely a driver of cancer cell phenotypes, (ii) overexpression of APE1 does not readily promote cellular transformation, and (iii) haploinsufficiency at the APE1 locus can have profound cellular consequences, consistent with BER playing a critical role in proliferating cells. Environ. Mol. Mutagen., 2017. © 2017 Wiley Periodicals, Inc.
Source: Environmental and Molecular Mutagenesis - Category: Molecular Biology Authors: Tags: Research Article Source Type: research