抄録
Cells exposed to Ionizing radiation, UV light and some chemotherapeutic compounds are prone to the formation of DNA-protein crosslinks (DPCs) in their genome. DPCs are detrimental or even lethal to cells. Recently, we have shown that homologous recombination (HR) and nucleotide excision repair (NER) collaborate to tolerate or repair DPCs. Here we further characterized the repair and tolerance mechanisms of DPCs. We found that the damage tolerance mechanism involving HR and subsequent replication restart (RR) provides the most effective means of cell survival against DPCs. Translesion synthesis does not serve as an alternative damage tolerance mechanism for DPCs in cell survival. Elimination of DPCs from the genome primarily relies on NER, which provides a second and moderately effective means of cell survival against DPCs. Interestingly, Cho rather than UvrC seems to be an effective nuclease for the NER of DPCs. Independently of the repair of DPCs, DNA glycosylases mitigate azaC toxicity, presumably by removing 5-azacytosine or its degradation product from the chromosome. Finally, topA may have a role in the repair of FA-induced DPCs.
