Data/hora: 06/06/2024 08:09:13

Provedor de dados: | 5
País: | France
Título: | Mechanistic insight into cadmium-induced inactivation of the Bloom protein
Autores: | Qin, Wei; Bazeille, Nicolas; Henry, Etienne; Zhang, Bo; Deprez, Eric; Xi, Xu-guang.
Data: | 2016-05
Ano: | 2016
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.
Tipo: | Text
Idioma: | Inglês

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/

Editor: | Nature Publishing Group
Formato: | application/pdf
Fonte: | Scientific Reports (2045-2322) (Nature Publishing Group), 2016-05 , Vol. 6 , N. 26225 , P. 12p.

Fonte:

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

info:eu-repo/semantics/openAccess

restricted use