FN Archimer Export Format
PT J
TI Mechanistic insight into cadmium-induced inactivation of the Bloom protein
BT 
AF QIN, Wei
   BAZEILLE, Nicolas
   HENRY, Etienne
   ZHANG, Bo
   DEPREZ, Eric
   XI, Xu-Guang
AS 1:1;2:2;3:2;4:1;5:2;6:1,2;
FF 1:;2:;3:;4:;5:;6:;
C1 Northwest A&F Univ, Coll Life Sci, Yangling 712100, Shaanxi, Peoples R China.
   Univ Paris Saclay, ENS Cachan, IDA FR3242, LBPA,CNRS UMR8113, F-94235 Cachan, France.
C2 NAWFU, CHINA
   UNIV PARIS SACLAY, FRANCE
SI https://w3.ifremer.fr/archimer-admin/author.jsp#
IN DOAJ
IF 4.259
TC 13
UR https://archimer.ifremer.fr/doc/00341/45196/44599.pdf
   https://archimer.ifremer.fr/doc/00341/45196/44600.pdf
LA English
DT Article
AB 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.
PY 2016
PD MAY
SO Scientific Reports
SN 2045-2322
PU Nature Publishing Group
VL 6
IS 26225
UT 000376132800001
DI 10.1038/srep26225
ID 45196
ER

EF