DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model.

ABSTRACT: The Polb gene encodes DNA polymerase beta (Pol β), a DNA polymerase that functions in base excision repair (BER) and microhomology-mediated end-joining. The Pol β-Y265C protein exhibits low catalytic activity and fidelity, and is also deficient in microhomology-mediated end-joining. We have previously shown that the Polb^Y265C/+ and Polb^Y265C/C mice develop lupus. These mice exhibit high levels of antinuclear antibodies and severe glomerulonephritis. We also demonstrated that the low catalytic activity of the Pol β-Y265C protein resulted in accumulation of BER intermediates that lead to cell death. Debris released from dying cells in our mice could drive development of lupus. We hypothesized that deletion of the Neil1 and Ogg1 DNA glycosylases that act upstream of Pol

SUBMITTER: Paluri SL 

PROVIDER: S-EPMC8635285 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature