The midblastula transition in Xenopus embryos activates multiple pathways to prevent apoptosis in response to DNA damage

Apoptosis is controlled by a complex interplay between regulatory proteins. Previous work has shown that Xenopus embryos remove damaged cells by apopt osis when irradiated before, but not after, the midblastula transition (MET ). Here we demonstrate that Akt/protein kinase B is activated and mediates an antiapoptotic signal only in embryos irradiated after the MET. In additi on, an increase in xBcl-2/xBax oligomerization and a decrease in xBax homod imerization promote a protective effect against apoptosis only after the ME T. The post-MET survival mechanism arrests cells in G(1) phase by increasin g expression of the cyclin-dependent kinase inhibitor p27(Xic1). p27(Xic1) associates with cyclin D/Cdk4 and cyclin A/Cdk2 complexes to cause G(1)/S a rrest, perhaps allowing more time for DNA repair. Taken together, the resul ts define the DNA damage response as an element of the MET and indicate tha t multiple mechanisms prevent apoptosis after the MBT.