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Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis
Author(s) -
Wroble Brian N.,
Sible Jill C.
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20449
Subject(s) - checkpoint kinase 2 , biology , xenopus , dna damage , microbiology and biotechnology , chek1 , g2 m dna damage checkpoint , cell cycle checkpoint , apoptosis , kinase , cell cycle , dna , genetics , gene
Early Xenopus laevis embryos possess cell cycles that do not arrest at checkpoints in response to damaged DNA. At the midblastula transition (MBT), embryos with damaged DNA undergo apoptosis. After the MBT, DNA damage triggers cell cycle arrest rather than apoptosis. The transition from checkpoint‐unregulated to checkpoint‐regulated cycles makes Xenopus embryos compelling for studying mechanisms regulating response to genomic damage. The DNA damage checkpoint is mediated by the Chk2/Cds1 kinase. Conflicting evidence implicates Chk2 as an inhibitor or promoter of apoptosis. To better understand the developmental function of Chk2, we expressed wild‐type (wt) and dominant‐negative (DN) Chk2 in Xenopus embryos. Wt‐Chk2 created a pre‐MBT checkpoint due to degradation of Cdc25A and phosphorylation of cyclin‐dependent kinases. Embryos expressing DN‐Chk2 developed normally until gastrulation and then underwent apoptosis. Conversely, low doses of wt‐Chk2 blocked radiation‐induced apoptosis. Therefore, Chk2 operates at a switch between cell cycle arrest or apoptosis in response to genomic assaults. Developmental Dynamics 233:1359–1365, 2005. © 2005 Wiley‐Liss, Inc.