Cadmium inhibits human DNA mismatch repair in vivo

Anne Lützen; Sascha Emilie Liberti; Lene Juel Rasmussen

doi:10.1016/j.bbrc.2004.06.102

Cadmium inhibits human DNA mismatch repair in vivo

Anne Lützen, Sascha Emilie Liberti, Lene Juel Rasmussen

64 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Biochemical and Biophysical Research Communications
Vol/bind	321
Udgave nummer	1
Sider (fra-til)	21-5
Antal sider	5
ISSN	0006-291X
DOI	https://doi.org/10.1016/j.bbrc.2004.06.102
Status	Udgivet - 13 aug. 2004
Udgivet eksternt	Ja

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10.1016/j.bbrc.2004.06.102

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@article{b1e345ed58fc46f3a5a0e4657089245d,

title = "Cadmium inhibits human DNA mismatch repair in vivo",

abstract = "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.",

keywords = "Alkylation, Base Pair Mismatch, Base Sequence, Cadmium Chloride, Carcinogens, Cations, Divalent, Cell Cycle, Cell Line, DNA, DNA Damage, DNA Repair, DNA Repair Enzymes, Deoxyribonucleases, Exodeoxyribonucleases, Humans, Kidney, Kinetics, Oligodeoxyribonucleotides",

author = "Anne L{\"u}tzen and Liberti, {Sascha Emilie} and Rasmussen, {Lene Juel}",

year = "2004",

month = aug,

day = "13",

doi = "10.1016/j.bbrc.2004.06.102",

language = "English",

volume = "321",

pages = "21--5",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier",

number = "1",

}

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

SN - 0006-291X

VL - 321

SP - 21

EP - 25

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

Cadmium inhibits human DNA mismatch repair in vivo

Abstract

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