Chromatin replication through cellular proliferation in eukaryotic cells

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A newly replicated DNA is assembled into nucleosome soon after the passage of replication fork. This rapid formation of nucleosome is functionally linked to DNA replication and plays a critical role for the maintenance of genome integrity in proliferating cells (Shibahara and Stillman, Cell, 1999). Two histone-binding proteins, CAF-1 and ASF1, are assumed to be involved in some process of this replication-coupled nucleosome assembly reaction.Using CAF-1-deficient chicken DT40 cell lines, we had recently shown that without CAF-1 and/or ASF1 function, S-phase progression was delayed and a rapid nucleosome assembly during DNA replication was disturbed in vivo. (Sanematsu, et al., J.Biol.Chem., 2006). This is the first direct evidence for the involvement of CAF-1 and ASF1 in a rapid nucleosome assembly during DNA replication in vivo. In addition, we obtained some interesting evidence for that CAF-1 is involved in Chk1-dependent checkpoint pathway after the treatment with HU (Takami et al., … More Mol.Biol.Cell, 2007).The loss-of-function mutants of caf-1 (fas) in Arabidopsis displayed severely disturbed cellular and functional organization of both meristems (Kaya et al., Cell, 2001). We also had shown that transcriptional gene silencing (TGS) of endogenous CACTA transposons was released infrequently in a stochastic manner in fas mutants without decreasing DNA methylation. Other endogenous silent genes at different chromosomal sites were also transcriptionally activated non-concomitantly with each other. Furthermore, TGS of the silent transgene β-glucuronidase (GUS) was also de-repressed randomly in fas mutants, irrespectively of developmental abnormalities, and the activated state of GUS was maintained during growth to produce clusters of cells expressing GUS (Ono et al., Genes Cells, 2006). Taken together, we strongly suggest that CAF-1 ensures stable maintenance of epigenetic states through multiple rounds of cell divisions and that defects in CAF-1 functions explain the stochastic occurrence of various phenotypes in the fas mutants. Less