Discovery of the mitotic selective chromatid segregation phenomenon and its implications for vertebrate development.

The asymmetric cell division process is required for cellular differentiation and embryonic development. Recent evidence obtained in Drosophila and C. elegans suggest that this process occurs by non-equivalent distribution of proteins or mRNA (intrinsic factors) to daughter cells, or by their differential exposure to cell extrinsic factors. In contrast, haploid fission yeast sister cells developmentally differ by inheriting sister chromatids that are differentiated by epigenetic means. Specifically, the act of DNA replication at the mating-type locus in yeast switches it's alternate alleles only in one specific member of chromosome 2 sister chromatids in nearly every chromosome replication cycle. To employ this kind of mechanism for cellular differentiation, strictly based on Watson-Crick structure of DNA in diploid organism, selective segregation mechanism is required to coordinate distribution of potentially differentiated sister chromatids to daughter cells. Genetic evidence to this postulate was fortuitously provided by the analysis of mitotic recombinants of chromosome 7 in mouse cells. Remarkably, the biased segregation occurs in some cell types but not in others and the process seems to be chromosome-specific. This review summarizes the discovery of selective chromatid segregation phenomenon and it suggests that such a process of Somatic Sister chromatid Imprinting and Selective chromatid Segregation (SSIS model) might explain development in eukaryotes, such as that of the body axis left-right visceral organs laterality specification in mice.

Rtf1-mediated eukaryotic site-specific replication termination.

The molecular mechanisms mediating eukaryotic replication termination and pausing remain largely unknown. Here we present the molecular characterization of Rtf1 that mediates site-specific replication termination at the polar Schizosaccharomyces pombe barrier RTS1. We show that Rtf1 possesses two chimeric myb/SANT domains: one is able to interact with the repeated motifs encoded by the RTS1 element as well as the elements enhancer region, while the other shows only a weak DNA binding activity. In addition we show that the C-terminal tail of Rtf1 mediates self-interaction, and deletion of this tail has a dominant phenotype. Finally, we identify a point mutation in Rtf1 domain I that converts the RTS1 element into a replication barrier of the opposite polarity. Together our data establish that multiple protein DNA and protein-protein interactions between Rtf1 molecules and both the repeated motifs and the enhancer region of RTS1 are required for site-specific termination at the RTS1 element.