Ionizing radiation induces apoptosis and elevates cyclin A1-Cdk2 activity before but not after the midblastula transition in Xenopus.
After the twelfth cell division in Xenopus embryos, zygotic gene transcription is activated, cells become motile, and cell division becomes asynchronous. This developmental change is termed the midblastula transition. High doses of gamma-irradiation (gamma-IR) before the midblastula transition induced apoptotic cell death and increased the levels of cyclin A1 and cyclin A1-Cdk2 activity. The addition of recombinant cyclin A1-Cdk2 induced the formation of apoptotic nuclei in Xenopus egg extracts, suggesting a role for cyclin A1-Cdk2 in apoptosis. Hallmarks of apoptosis, such as internucleosomal DNA fragmentation, pyknotic and uniformly condensed nuclei, and loss of intercellular attachments, were evident in embryos exposed to gamma-IR before the midblastula transition. Apoptotic cells accumulated in the blastocoel, suggesting that before the midblastula transition Xenopus embryos use apoptosis to eliminate cells containing damaged DNA. However, embryos treated with the same dose of gamma-IR after the midblastula transition developed normally and exhibited no signs of apoptosis, no change in cyclin A1 level, and no increase in cyclin A1-Cdk2 activity. These results indicate that there is a change in the response to DNA damage at the midblastula transition in Xenopus embryos.
Anderson
J A
JA
Howard Hughes Medical Institute, University of Colorado School of Medicine, Denver 80262, USA.
Lewellyn
A L
AL
Maller
J L
JL
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001755:Blastocyst / Q000378:metabolism / Q000528:radiation effects*; D042846:CDC2-CDC28 Kinases; D002467:Cell Nucleus / Q000187:drug effects; D019925:Cyclin A; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism / Q000528:radiation effects*; D016213:Cyclins / Q000378:metabolism / Q000528:radiation effects*; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D010063:Ovum / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000528:radiation effects*; D014158:Transcription, Genetic / Q000528:radiation effects; D014981:Xenopus; D029867:Xenopus Proteins; D015053:Zygote / Q000378:metabolism / Q000528:radiation effects
D019925:Cyclin A; D016213:Cyclins; D029867:Xenopus Proteins; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495891:Cdk2 protein, Xenopus; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases