Cadmium inhibits human DNA mismatch repair in vivo.
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.
Lützen
Anne
A
Department of Life Sciences and Chemistry, Roskilde University, DK-4000 Roskilde, Denmark.
Liberti
Sascha Emilie
SE
Rasmussen
Lene Juel
LJ
D000478:Alkylation; D020137:Base Pair Mismatch / Q000187:drug effects*; D001483:Base Sequence; D019256:Cadmium Chloride / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D002413:Cations, Divalent / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D045643:DNA Repair Enzymes; D003851:Deoxyribonucleases / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D007668:Kidney; D007700:Kinetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
D002273:Carcinogens; D002413:Cations, Divalent; D009838:Oligodeoxyribonucleotides; D004247:DNA; D003851:Deoxyribonucleases; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; D045643:DNA Repair Enzymes; D019256:Cadmium Chloride