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10.07.17 Chk1 orchestrates regulation of cell cycle length at mid-blastula transition by inhibiting Drf1

last modified Jul 11, 2017 10:47 AM
In this Dev Cell paper the Zegerman lab, with collaborator Jim Smith at the Crick, describe a role for checkpoint kinase Chk1 in the mid-blastula transition in Xenopus

Chk1 inhibition of the replication factor Drf1 guarantees cell cycle elongation at the Xenopus laevis mid-blastula transition

Collart C, Smith JC and Zegerman P (2017) Dev Cell Volume 42, Issue 1, p82–96.e3,  DOI: 10.1016/j.devcel.2017.06.010

 

Highlights from the paper

  • Activation of Chk1 at the Xenopus MBT results in the degradation of Drf1
  • Drf1 degradation is SCFβ-TRCP dependent
  • Chk1 blocks the cell cycle in the early embryo through inhibition of Drf1
  • Inhibition of Drf1 is an essential function of Chk1 during gastrulation

 

Authors' summary

The early cell divisions of many embryos are unusual, in that they are very rapid and occur in the near absence of RNA synthesis. At the so-called mid-blastula transition (MBT), however, the cell cycle elongates, and RNA synthesis begins.

In previous work we provided support for a model in which the MBT is triggered by the progressive titration of regulatory proteins by increasing numbers of nuclei. We now show that the timing of the MBT is made more precise through the activation of the checkpoint kinase Chk1. Working through the E3 ubiquitin ligase SCFb-TRCP, activated Chk1 causes the destruction of Drf1, one of the proteins known to regulate the MBT.

The work defines one of the functions of Chk1 during embryogenesis and it confirms Drf1 as a key player in the regulation of the early cell cycle. It also provides an intriguing ‘fail-safe’ mechanism, in which nuclear titration is accompanied by the selective destruction of Drf1.

 

 

Read more about research in the Zegerman lab

Watch Phil Zegerman describe his research on replication initiation

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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