The development of many organisms is accompanied by
changes in the density and timing of replication initiation events during the
cell cycle. How and why the rates of DNA replication initiation are regulated
remains poorly understood. Thirty years ago it was proposed that the
lengthening of the cell cycle at the mid-blastula transition (MBT) of the
African clawed toad Xenopus laevis is caused by titration of replication
initiation factors by the increasing nuclear/cytoplasmic ratio. Here I will
present work that shows that four essential replication factors, Cut5, RecQ4,
Treslin and Drf1 are limiting for initiation in vitro in Xenopus egg
extracts. Over-expression of these factors in eggs causes an increase in origin
density and a shortening of the cell cycle at the MBT. Together with nucleotide
levels we demonstrate the central role of these limiting components in the
developmental activation of the DNA damage checkpoint. Finally we show for the
first time specifically that regulating origin density is essential for
embryonic development. Together with our previous work in budding yeast we
address a long-standing question in development and will present a potentially
unifying model for how organisms regulate S-phase length.

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Last updated: Wednesday, 24 October 2012