Abstract
Radiation produces various types of DNA lesions including oxidized bases, strand breaks, DNA-protein cross-links (DPCs), and interstrand cross-links (ISCs). DPCs and ISCs are also produced by exposure to aldehyde and platinum compounds. As contrasted with the repair mechanisms of oxidized bases and strand breaks, those of DPCs and ISCs have been poorly elucidated. DPCs are unique in that a bulky DPC protein is covalently bonded to DNA and hence could impair the access of factors involved in DNA transactions such as replication, transcription, and repair. We have investigated the repair mechanism of DPCs in prokaryotic cells. The in vitro damage-excising activity of UvrABC varied significantly depending on the size of DPC proteins. Furthermore, studies with repair-deficient E. coli cells show that nucleotide excision repair (NER) and recombinational repair are involved in the in vivo repair of DPCs. In the present study, we analyzed the sensitivity of human cells to formaldehyde (FA) and 5-aza-2'-deoxycytidine (AZC). FA produces a covalent bond between a base and protein, and AZC is incorporated into DNA to produce a covalent bond between 5-azacytosine and CpG methyltransferase. Cells were treated with the DPC-inducing agents and cell viability was measured by colony formation. etailed data and discuss the possible repair mechanism in human cells.
