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Zygotic Genome Activation Triggers the DNA Replication Checkpoint at the Midblastula Transition

Author(s): Blythe, Shelby A; Wieschaus, Eric F

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Abstract: A conserved feature of the midblastula transition (MBT) is a requirement for a functional DNA replication checkpoint to coordinate cell cycle remodeling and zygotic genome activation (ZGA). We have investigated what triggers this checkpoint during Drosophila embryogenesis. We find that the magnitude of the checkpoint scales with the quantity of transcriptionally engaged DNA. Measuring RNA Polymerase II (Pol II) binding at 20-minute intervals over the course of ZGA reveals that the checkpoint coincides with widespread de novo recruitment of Pol II that precedes and does not require a functional checkpoint. This recruitment drives slowing or stalling of DNA replication at transcriptionally engaged loci. Reducing Pol II recruitment in zelda mutants both reduces replication stalling and bypasses the requirement for a functional checkpoint. This suggests a model where the checkpoint functions as a feedback mechanism to remodel the cell cycle in response to nascent ZGA.
Publication Date: 12-Mar-2015
Electronic Publication Date: 5-Mar-2015
Citation: Blythe, Shelby A, Wieschaus, Eric F. (2015). Zygotic Genome Activation Triggers the DNA Replication Checkpoint at the Midblastula Transition. Cell, 160 (6), 1169 - 1181. doi:10.1016/j.cell.2015.01.050
DOI: doi:10.1016/j.cell.2015.01.050
ISSN: 0092-8674
Pages: 1169 - 1181
Type of Material: Journal Article
Journal/Proceeding Title: Cell
Version: Author's manuscript

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