Nuclear import of p53 during Xenopus laevis early development in relation to DNA replication and DNA repair

Abstract

The role of p53 in transcriptional activation of genes involved in cell cycle progression is well established. However, the wide range of functions attributed to this gene suggests that some of them might be unrelated to transcription. Here we investigated p53 localization and recruitment to chromatin during Xenopus early development when 12 rapid cell cycles occur without transcription of the genome. We show that after fertilization, part of the large store of p53 previously stored in the cytoplasm of the oocyte is imported into the nucleus. This import was further analyzed in relation with DNA replication and DNA repair using cell-free systems from Xenopus eggs. Formation of a nuclear lamina envelope is necessary for the import of p53 into the nucleus. p53 associates both with decondensed DNA and the nuclear lamina envelope, but no colocalization with prereplication or replication complexes is observed. We show that UV- or gamma-damaged nuclei recruit p53 as well as replication protein A (RPA) in large common foci. Together, these data suggest that p53 plays a role in the regulation of the accelerated S phases that occur during Xenopus early development, in a manner that does not rely on its transcription-mediated activity.