Pharmacology, Toxicology and Environmental Health Commons^™

Inhibition Of Rad18 By Arsenic, Lindsay B. Volk

Biomedical Sciences ETDs

Arsenite exposure leads to the retention of UV-induced DNA damage, thus burdening translesion synthesis (TLS). Rad18 is an essential factor in initiating TLS through PCNA monoubiquitination and is implicated in homologous recombination. It contains two functionally and structurally distinct zinc fingers that are potential targets for arsenite binding. Results from this study reveal arsenite binding to both zinc fingers of Rad18 and a corresponding loss of domain function. Importantly, arsenite inhibited Rad18 RING-dependent PCNA monoubiquitination and polymerase eta recruitment to DNA damage. Further analysis demonstrated multiple effects of arsenite, including the reduction in the nuclear localization and UV-induced chromatin recruitment …

Developmental Effects Of Chronic Low-Level Arsenic Exposure In Mouse Embryonic Stem Cells And In Human Induced Pluripotent Stem Cells, M. Chiara Perego

All Dissertations

Arsenic is an environmental contaminant commonly found in food and drinking water. Exposure to arsenic during embryonic development has been linked to reduced muscle growth, disrupted muscle development and locomotor activity, impaired neurodevelopment, reduced IQ, impaired memory and learning deficits. While the mechanisms responsible for developmental changes following in utero exposure to arsenic are not well known, one possibility is that arsenic might disrupt proper cellular differentiation. Therefore, we aimed to investigate the mechanisms by which arsenic exposure could alter stem cell differentiation into neurons.

First, we continuously exposed P19 mouse embryonic stem (ES) cells to 0.1 μM (7.5 ppb) …