DNA Polymerase Beta is Critical for Cell Survival and Genomic Stability in Mice

Postdoctoral Associate
15 York St, New Haven, CT 06510-3221

DNA polymerase β (pol β) is known to be a key player in the base excision repair pathway and mice devoid of DNA pol β do not live beyond a few hours after birth. Y265C pol β variant has been shown to be a strong mutator polymerase as well as a slow DNA polymerase. Mice expressing Y265C pol β are born at normal Mendelian ratios. However, they are small and 60% die within a few hours after birth. Slow proliferation and significantly increased levels of cell death are observed in many organs of the E14 homozygous embryos compared to wild type littermates.

Mouse embryo fibroblasts (MEFs) prepared from the Y265C pol β embryos proliferate at a rate slower than wt cells and exhibit a gap-filling deficiency during base excision repair. As a result of this, chromosomal
aberrations, and single- and double-strand breaks are present at significantly higher levels in the homozygous mutant versus wild-type MEFs. Our data demonstrate that the DNA polymerase activity of pol β is
essential for survival and genome stability.