An onset model of mutually catalytic self-replicative systems formed by an assembly of polynucleotides

Self-replicability is the unique attribute observed in all the living organisms and the question how the life was physically initiated could be equivalent to the question how self-replicating informative polymers were formed in the abiotic material world. It has been suggested that the present DNA and proteins world was preceded by RNA world in which genetic information of RNA molecules was replicated by the mutual catalytic function of RNA molecules. However, the important question how the transition occurred from a material world to the very early pre-RNA world remains unsolved experimentally nor theoretically. We present an onset model of mutually catalytic self-replicative systems formed in an assembly of polynucleotides. A quantitative expression of the critical condition for the onset of growing fluctuation towards self-replication in this model is obtained by analytical and numerical calculations.Comment: 13 pages, 10 figures. Accepted for publication in Physical Review

A global profile of replicative polymerase usage

Three eukaryotic DNA polymerases are essential for genome replication. Polymerase (Pol) α–primase initiates each synthesis event and is rapidly replaced by processive DNA polymerases: Polɛ replicates the leading strand, whereas Polδ performs lagging-strand synthesis. However, it is not known whether this division of labor is maintained across the whole genome or how uniform it is within single replicons. Using Schizosaccharomyces pombe, we have developed a polymerase usage sequencing (Pu-seq) strategy to map polymerase usage genome wide. Pu-seq provides direct replication-origin location and efficiency data and indirect estimates of replication timing. We confirm that the division of labor is broadly maintained across an entire genome. However, our data suggest a subtle variability in the usage of the two polymerases within individual replicons. We propose that this results from occasional leading-strand initiation by Polδ followed by exchange for Polɛ

GATA3 mediates nonclassical β-catenin signaling in skeletal cell fate determination and ectopic chondrogenesis

Skeletal precursors are mesenchymal in origin and can give rise to distinct sublineages. Their lineage commitment is modulated by various signaling pathways. The importance of Wnt signaling in skeletal lineage commitment has been implicated by the study of β-catenin-deficient mouse models. Ectopic chondrogenesis caused by the loss of β-catenin leads to a long-standing belief in canonical Wnt signaling that determines skeletal cell fate. As β-catenin has other functions, it remains unclear whether skeletogenic lineage commitment is solely orchestrated by canonical Wnt signaling. The study of the Wnt secretion regulator Gpr177/Wntless also raises concerns about current knowledge. Here, we show that skeletal cell fate is determined by β-catenin but independent of LEF/TCF transcription. Genomic and bioinformatic analyses further identify GATA3 as a mediator for the alternative signaling effects. GATA3 alone is sufficient to promote ectopic cartilage formation, demonstrating its essential role in mediating nonclassical β-catenin signaling in skeletogenic lineage specification

欧米のコンプライアンスと企業倫理の企業統治的研究

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