DNA-Protein Crosslinks in Nucleosome Core Particles: Formation and Biological Consequences
【摘要】：Nucleosome core particle(NCP) is the fundamental unit of genome DNA in eukaryotic cells. Recently studies have revealed that DNA damage and repair processes in NCP are much more complicated than in native DNA duplex. Histones can catalyze or retard the DNA damage and repair through different mechanism in NCPs. In the present study, we showed that some DNA damage intermediates lead to DNA-histone crosslinks. One example is that 5-formylcytosine(5 fC), which is thought to be a DNA demethylation intermediate, yields essential DNA-protein crosslink(DPC) in NCPs. This DPC form via C=N bond between the formyl function of 5 fC and primary amino groups on histones, and thus exist in in dynamic equilibrium. Another example is that OG~(ox), a DNA damage intermediate produced by oxidation of 8-oxoguanine(8-oxo-G), leads to DPC quantitatively. This type of DPC is stable and cannot repaired by DNA glycosylase hOGG1. These results suggest that DPCs formations in NCPs are common biological events and much remains to be learned about their biological consequences.