Mechanistic insight into cadmium-induced inactivation of the Bloom protein.

ABSTRACT: Cadmium is a toxic metal that inactivates DNA-repair proteins via multiple mechanisms, including zinc substitution. In this study, we investigated the effect of Cd(2+) on the Bloom protein (BLM), a DNA-repair helicase carrying a zinc-binding domain (ZBD) and playing a critical role to ensure genomic stability. One characteristics of BLM-deficient cells is the elevated rate of sister chromatid exchanges, a phenomenon that is also induced by Cd(2+). Here, we show that Cd(2+) strongly inhibits both ATPase and helicase activities of BLM. Cd(2+) primarily prevents BLM-DNA interaction via its binding to sulfhydryl groups of solvent-exposed cysteine residues and, concomitantly, promotes the formation of large BLM multimers/aggregates. In contrast to previously described Cd(2+) effects on other zi

SUBMITTER: Qin W 

PROVIDER: S-EPMC4872126 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature