Cadmium inhibits human DNA mismatch repair in vivo
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Cadmium inhibits human DNA mismatch repair in vivo. / Lützen, Anne; Liberti, Sascha Emilie; Rasmussen, Lene Juel.
In: Biochemical and Biophysical Research Communications, Vol. 321, No. 1, 13.08.2004, p. 21-5.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cadmium inhibits human DNA mismatch repair in vivo
AU - Lützen, Anne
AU - Liberti, Sascha Emilie
AU - Rasmussen, Lene Juel
PY - 2004/8/13
Y1 - 2004/8/13
N2 - 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.
AB - 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.
KW - Alkylation
KW - Base Pair Mismatch
KW - Base Sequence
KW - Cadmium Chloride
KW - Carcinogens
KW - Cations, Divalent
KW - Cell Cycle
KW - Cell Line
KW - DNA
KW - DNA Damage
KW - DNA Repair
KW - DNA Repair Enzymes
KW - Deoxyribonucleases
KW - Exodeoxyribonucleases
KW - Humans
KW - Kidney
KW - Kinetics
KW - Oligodeoxyribonucleotides
U2 - 10.1016/j.bbrc.2004.06.102
DO - 10.1016/j.bbrc.2004.06.102
M3 - Journal article
C2 - 15358209
VL - 321
SP - 21
EP - 25
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -
ID: 119639148