title: Titration of four replication factors is essential for the Xenopus laevis midblastula transition.
abstract: The rapid, reductive early divisions of many metazoan embryos are followed by the midblastula transition (MBT), during which the cell cycle elongates and zygotic transcription begins. It has been proposed that the increasing nuclear to cytoplasmic (N/C) ratio is critical for controlling the events of the MBT. We show that four DNA replication factors--Cut5, RecQ4, Treslin, and Drf1--are limiting for replication initiation at increasing N/C ratios in vitro and in vivo in Xenopus laevis. The levels of these factors regulate multiple events of the MBT, including the slowing of the cell cycle, the onset of zygotic transcription, and the developmental activation of the kinase Chk1. This work provides a mechanism for how the N/C ratio controls the MBT and shows that the regulation of replication initiation is fundamental for normal embryogenesis.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Clara
authors.initials: C
authors.lastname: Collart
authors.forename: George E
authors.initials: GE
authors.lastname: Allen
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bradshaw
authors.forename: James C
authors.initials: JC
authors.lastname: Smith
authors.forename: Philip
authors.initials: P
authors.lastname: Zegerman
mesh_terms: D000818:Animals; D036703:Blastula / Q000196:embryology* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins; D053484:RecQ Helicases / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C505573:DBF4B protein, Xenopus; D004268:DNA-Binding Proteins; C547407:TICRR protein, Xenopus; C509993:TopBP1 protein, Xenopus; D029867:Xenopus Proteins; D053484:RecQ Helicases
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