| Registro completo |
| Provedor de dados: |
ArchiMer
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| País: |
France
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| Título: |
Mechanistic insight into cadmium-induced inactivation of the Bloom protein
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| Autores: |
Qin, Wei
Bazeille, Nicolas
Henry, Etienne
Zhang, Bo
Deprez, Eric
Xi, Xu-guang
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| Data: |
2016-05
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| Ano: |
2016
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| Resumo: |
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 Cd2+ effects on other zinc-containing DNA-repair proteins, the ZBD appears to play a minor role in the Cd2+-mediated inhibition. While the Cd2+-dependent formation of inactive multimers and the defect of DNA-binding were fully reversible upon addition of EDTA, the inhibition of the DNA unwinding activity was not counteracted by EDTA, indicating another mechanism of inhibition by Cd2+ relative to the targeting of a catalytic residue. Altogether, our results provide new clues for understanding the mechanism behind the ZBD-independent inactivation of BLM by Cd2+ leading to accumulation of DNA double-strand breaks.
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| Tipo: |
Text
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| Idioma: |
Inglês
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| Identificador: |
https://archimer.ifremer.fr/doc/00341/45196/44599.pdf
https://archimer.ifremer.fr/doc/00341/45196/44600.pdf
DOI:10.1038/srep26225
https://archimer.ifremer.fr/doc/00341/45196/
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| Editor: |
Nature Publishing Group
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| Formato: |
application/pdf
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| Fonte: |
Scientific Reports (2045-2322) (Nature Publishing Group), 2016-05 , Vol. 6 , N. 26225 , P. 12p.
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| Direitos: |
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info:eu-repo/semantics/openAccess
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