Geminin Deficiency Causes a Chk1-dependent G2 Arrest inXenopus
- 1 October 2002
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 13 (10), 3662-3671
- https://doi.org/10.1091/mbc.e02-04-0199
Abstract
Geminin is an unstable inhibitor of DNA replication that gets destroyed at the metaphase/anaphase transition. The biological function of geminin has been difficult to determine because it is not homologous to a characterized protein and has pleiotropic effects when overexpressed. Geminin is thought to prevent a second round of initiation during S or G2 phase. In some assays, geminin induces uncommitted embryonic cells to differentiate as neurons. In this study, geminin was eliminated from developing Xenopus embryos by using antisense techniques. Geminin-deficient embryos show a novel and unusual phenotype: they complete the early cleavage divisions normally but arrest in G2 phase immediately after the midblastula transition. The arrest requires Chk1, the effector kinase of the DNA replication/DNA damage checkpoint pathway. The results indicate that geminin has an essential function and that loss of this function prevents entry into mitosis by a Chk1-dependent mechanism. Geminin may be required to maintain the structural integrity of the genome or it may directly down-regulate Chk1 activity. The data also show that during the embryonic cell cycles, rereplication is almost entirely prevented by geminin-independent mechanisms.Keywords
This publication has 39 references indexed in Scilit:
- Control of DNA Replication and Chromosome Ploidy by Geminin and Cyclin AMolecular and Cellular Biology, 2002
- The Drosophila Geminin homolog: roles for Geminin in limiting DNA replication, in anaphase and in neurogenesisGenes & Development, 2001
- Activation of the DNA Replication Checkpoint Through RNA Synthesis by PrimaseScience, 2000
- Regulation of Chromosome ReplicationAnnual Review of Biochemistry, 2000
- How Proteolysis Drives the Cell CycleScience, 1996
- Mitosis in transitionCell, 1994
- Human cdc2 protein kinase is a major cell-cycle regulated tyrosine kinase substrateNature, 1988
- A role for the nuclear envelope in controlling DNA replication within the cell cycleNature, 1988
- A major developmental transition in early xenopus embryos: II. control of the onset of transcriptionCell, 1982
- A major developmental transition in early xenopus embryos: I. characterization and timing of cellular changes at the midblastula stageCell, 1982