Cadmium inhibits human DNA mismatch repair in vivo

被引:68
作者
Lützen, A [1 ]
Liberti, SE [1 ]
Rasmussen, LJ [1 ]
机构
[1] Roskilde Univ, Dept Chem & Life Sci, DK-4000 Roskilde, Denmark
关键词
hEXO1; hMSH2; DNA mismatch repair; cancer; cadmium;
D O I
10.1016/j.bbrc.2004.06.102
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The heavy metal cadmium (Cd) is a human carcinogen that inhibits DNA repairs activities. We show that DNA mismatch repair (MMR)-mediated cell cycle arrest after alkylation damage is suppressed by exposure to Cd and that this effect is reserved by preincubation with excess of zinc (Zn). We show that Cd-mediated inactivation of MMr activity is not caused by disruption of complex formation between the MMR proteins hEXO1-hMutSalpha and hEXO1-hMutSalpha nor does Cd inhibit 5'-exonuclease activity of hEXO1 in vitro. Thus, our studies show that exposure of human cells to Cd suppresses MMR activity, a repair known to play an important role in colon cancer and that this effect can be reversed by Zn treatment. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:21 / 25
页数:5
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