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Mechanistic insight into cadmium-induced inactivation of the Bloom protein ArchiMer
Qin, Wei; Bazeille, Nicolas; Henry, Etienne; Zhang, Bo; Deprez, Eric; Xi, Xu-guang.
Cadmium is a toxic metal that inactivates DNA-repair proteins via multiple mechanisms, including zinc substitution. In this study, we investigated the effect of Cd2+ 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 Cd2+. Here, we show that Cd2+ strongly inhibits both ATPase and helicase activities of BLM. Cd2+ 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...
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Ano: 2016 URL: https://archimer.ifremer.fr/doc/00341/45196/44599.pdf
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