PARP1 Inhibition Augments UVB-Mediated Mitochondrial Changes-Implications for UV-Induced DNA Repair and Photocarcinogenesis.

ABSTRACT: Keratinocytes provide the first line of defense of the human body against carcinogenic ultraviolet (UV) radiation. Acute and chronic UVB-mediated cellular responses were widely studied. However, little is known about the role of mitochondrial regulation in UVB-induced DNA damage. Here, we show that poly (ADP-ribose) polymerase 1 (PARP1) and ataxia-telangiectasia-mutated (ATM) kinase, two tumor suppressors, are important regulators in mitochondrial alterations induced by UVB. Our study demonstrates that PARP inhibition by ABT-888 upon UVB treatment exacerbated cyclobutane pyrimidine dimers (CPD) accumulation, cell cycle block and cell death and reduced cell proliferation in premalignant skin keratinocytes. Furthermore, in human keratinocytes UVB enhanced oxidative phosphorylation (OXPHOS) a

SUBMITTER: Hegedus C 

PROVIDER: S-EPMC7016756 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature