Abstract: Dynamics of epigenomic changes during development of embryos and germ cells in miceDevelopmental process is an excellent object of the study on epigenetic regulation of gene expression.We have been studying epigenomic states of early mouse embryos, various stem cells and primordial germ cells using three complementary approaches; visualization of global DNA methylation patterns in living cells, analysis of X chromosome inactivation/reactivation processes, and DNA methylation analysis of small number of cells.Based on knowledge obtained from these experiments, epigenetic reprogramming events taking place in the development of embryos and germ cells will be discussed. W1 -1IDE, Hiroshi 1 ( 1 Dept.Mathematical and Life Sci.s, Grad.Sch.Sci., Hiroshima Univ.)Repair and damage tolerance mechanisms for DNA-protein crosslinks DNA-protein crosslinks (DPCs) are formed when cells are exposed to ionizing radiation, UV light, and environmental toxic chemicals.DPCs are detrimental to cells since they inhibit DNA replication and transcription.Recently, we have shown that homologous recombination (HR) and nucleotide excision repair (NER) collaborate to mitigate the adverse effect of DPCs in E. coli.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.We are also investigating the repair mechanism of DPCs in mammalian cells. W1-2