Deregulated expression of DNA polymerase β is involved in the progression of genomic instability.

Environmental and Molecular Mutagenesis
Qingying LuoZunzhen Zhang

Abstract

Deregulated expression of DNA polymerase beta (pol β) has been implicated in genomic instability that leads to tumorigenesis, yet the mechanisms underlying the pol β-mediated genetic instability remain elusive. In this study, we investigated the roles of deregulated expression of pol β in spontaneous and xenobiotic-induced genetic instability using mouse embryonic fibroblasts (MEFs) that express distinct pol β levels (wild-type, null, and overexpression) as a model system. Three genetic instability endpoints, DNA strand breaks, chromosome breakage, and gene mutation, were examined under various expression levels of pol β by comet assay, micronuclei test, and hprt mutation assay. Our results demonstrate that neither pol β deficiency nor pol β overexpression is sufficient for accumulation of spontaneous DNA damage that promotes a hyperproliferation phenotype. However, pol β null cells exhibit increased sensitivity to exogenous DNA damaging agents with increased genomic instability compared with pol β wild-type and overexpression cells. This finding suggests that a pol β deficiency may underlie genomic instability induced by exogenous DNA damaging agents. Interestingly, pol β overexpression cells exhibit less chromosomal or DNA da...Continue Reading

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Citations

Jul 11, 2013·Journal of Skin Cancer·Scott F LindseyJames M Grichnik
Mar 11, 2017·Critical Reviews in Biochemistry and Molecular Biology·Alexandra Vaisman, Roger Woodgate
Jan 6, 2018·Biomedicines·Ilya O VelegzhaninovOlesya M Vakhrusheva
Jun 20, 2016·Oncotarget·Valeria SimonelliEugenia Dogliotti
Mar 7, 2017·Biological Trace Element Research·Hongyu ChenZunzhen Zhang
Nov 5, 2019·Nuclear Medicine and Biology·Zude ChenChangning Wang

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