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Cadmium inhibits human DNA mismatch repair in vivo

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The heavy metal cadmium (Cd) is a human carcinogen that inhibits DNA repair 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 reversed 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-hMutS alpha and hEXO1-hMutL alpha 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 activity known to play an important role in colon cancer and that this effect can be reversed by Zn treatment.

OriginalsprogEngelsk
TidsskriftBiochemical and Biophysical Research Communications
Vol/bind321
Udgave nummer1
Sider (fra-til)21-5
Antal sider5
ISSN0006-291X
DOI
StatusUdgivet - 13 aug. 2004
Eksternt udgivetJa

ID: 119639148