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Chk1 Inhibition of the Replication Factor Drf1 Guarantees Cell-Cycle Elongation at the Xenopus laevis Mid-blastula Transition

Published version
Peer-reviewed

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Authors

Collart, C 
Smith, JC 

Abstract

The early cell divisions of many metazoan embryos are rapid and occur in the near absence of transcription. At the mid-blastula transition (MBT), the cell cycle elongates and several processes become established including the onset of bulk transcription and cell-cycle checkpoints. How these events are timed and coordinated is poorly understood. Here we show in Xenopus laevis that developmental activation of the checkpoint kinase Chk1 at the MBT results in the SCFβTRCP-dependent degradation of a limiting replication initiation factor Drf1. Inhibition of Drf1 is the primary mechanism by which Chk1 blocks cell-cycle progression in the early embryo and is an essential function of Chk1 at the blastula-to-gastrula stage of development. This study defines the down-regulation of Drf1 as an important mechanism to coordinate the lengthening of the cell cycle and subsequent developmental processes.

Description

Keywords

DDK, Drf1, MBT, Xenopus laevis, cell cycle, checkpoint, chk1, midblastula transition, replication initiation, Amino Acid Sequence, Animals, Blastula, Cell Cycle, Checkpoint Kinase 1, Chromosomal Proteins, Non-Histone, DNA Replication, Down-Regulation, Embryo, Nonmammalian, Embryonic Development, Gene Expression Regulation, Developmental, Phosphorylation, Proteolysis, SKP Cullin F-Box Protein Ligases, Xenopus Proteins, Xenopus laevis, beta-Transducin Repeat-Containing Proteins

Journal Title

Developmental Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

42

Publisher

Cell Press
Sponsorship
Wellcome Trust (107056/Z/15/Z)
Worldwide Cancer Research (formerly AICR) (10-0908)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
The work was supported by Worldwide Cancer Research 10-0908, Wellcome Trust 107056/Z/15/Z, Gurdon Institute funding (Cancer Research UK C6946/A14492, Wellcome Trust 092096), and Francis Crick Institute funding (Cancer Research UK FC001-157, the UK Medical Research Council FC001-157, Wellcome Trust FC001-157).
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