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Developmental control of late replication and S phase length.


ABSTRACT: Fast, early embryonic cell cycles have correspondingly fast S phases. In early Drosophila embryos, forks starting from closely spaced origins replicate the whole genome in 3.4 min, ten times faster than in embryonic cycle 14 and a hundred times faster than in a wing disc. It is not known how S phase duration is regulated. Here we examined prolongation of embryonic S phases, its coupling to development, and its relationship to the appearance of heterochromatin.Imaging of fluorescent nucleotide incorporation and GFP-PCNA gave exquisite time resolution of S phase events. In the early S phases, satellite sequences replicated rapidly despite a compact chromatin structure. In S phases 11-13, a delay in satellite replication emerged in sync with modest and progressive prolongation of S phase. In S phase 14, major and distinct delays ordered the replication of satellites into a sequence that occupied much of S phase. This onset of late replication required transcription. Satellites only accumulated abundant heterochromatin protein 1 (HP1) after replicating in S phase 14. By cycle 15, satellites clustered in a compact HP1-positive mass, but replication occurred at decondensed foci at the surface of this mass.The slowing of S phase is an active process, not a titration of maternal replication machinery. Most sequences continue to replicate rapidly in successive cycles, but increasing delays in the replication of satellite sequences extend S phase. Although called constitutively heterochromatic, satellites acquire the distinctive features of heterochromatin, compaction, late replication, HP1 binding, and aggregation at the chromocenter, in successive steps coordinated with developmental progress.

SUBMITTER: Shermoen AW 

PROVIDER: S-EPMC3108027 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Developmental control of late replication and S phase length.

Shermoen Antony W AW   McCleland Mark L ML   O'Farrell Patrick H PH  

Current biology : CB 20101111 23


<h4>Background</h4>Fast, early embryonic cell cycles have correspondingly fast S phases. In early Drosophila embryos, forks starting from closely spaced origins replicate the whole genome in 3.4 min, ten times faster than in embryonic cycle 14 and a hundred times faster than in a wing disc. It is not known how S phase duration is regulated. Here we examined prolongation of embryonic S phases, its coupling to development, and its relationship to the appearance of heterochromatin.<h4>Results</h4>I  ...[more]

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