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XB-ART-6362
Mol Biol Cell 2002 Oct 01;1310:3662-71. doi: 10.1091/mbc.e02-04-0199.
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Geminin deficiency causes a Chk1-dependent G2 arrest in Xenopus.

McGarry TJ .


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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.

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Species referenced: Xenopus laevis
Genes referenced: cdc25c cdk1 cds1 chek1 gmnn myc pold1
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References [+] :
Blow, A role for the nuclear envelope in controlling DNA replication within the cell cycle. 1988, Pubmed, Xenbase