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 apoptosis 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 addition, an increase in xBcl-2/xBax oligomerization and a decrease in xBax homodimerization promote a protective effect against apoptosis only after the MET. The post-MET survival mechanism arrests cells in G(1) phase by increasing 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 arrest, perhaps allowing more time for DNA repair. Taken together, the results define the DNA damage response as an element of the MET and indicate that multiple mechanisms prevent apoptosis after the MBT.