title: Embryonic onset of late replication requires Cdc25 down-regulation.
abstract: The Drosophila midblastula transition (MBT), a major event in embryogenesis, remodels and slows the cell cycle. In the pre-MBT cycles, all genomic regions replicate simultaneously in rapid S phases that alternate with mitosis, skipping gap phases. At the MBT, down-regulation of Cdc25 phosphatase and the resulting inhibitory phosphorylation of the mitotic kinase Cdk1 create a G2 pause in interphase 14. However, an earlier change in interphase 14 is the prolongation of S phase. While the signals modifying S phase are unknown, the onset of late replication-where replication of constitutively heterochromatic satellite sequences is delayed-extends S-phase 14. We injected Cdc25 mRNA to bypass the developmentally programmed down-regulation of Cdc25 at the MBT. Introduction of either Cdc25 isoform (String or Twine) or enhanced Cdk1 activity triggered premature replication of late-replicating sequences, even after their specification, and thereby shortened S phase. Reciprocally, reduction of Cdk1 activity by knockdown of mitotic cyclins extended pre-MBT S phase. These findings suggest that high Cdc25 and Cdk1 contribute to the speed of the rapid, pre-MBT S phases and that down-regulation of these activities plays a broader role in MBT-associated changes than was previously suspected.
authors.affiliation: Department of Biochemistry, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Farrell
authors.forename: Antony W
authors.initials: AW
authors.lastname: Shermoen
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
authors.forename: Patrick H
authors.initials: PH
authors.lastname: O'Farrell
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication; D015536:Down-Regulation; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000201:enzymology* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008938:Mitosis; D016196:S Phase; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004247:DNA; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases