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.
| Original language | English |
|---|---|
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 321 |
| Issue number | 1 |
| Pages (from-to) | 21-5 |
| Number of pages | 5 |
| ISSN | 0006-291X |
| DOIs | |
| Publication status | Published - 13 Aug 2004 |
| Externally published | Yes |
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
