Distribution of p53 binding protein 1 (53BP1) and phosphorylated H2A.X during mouse preimplantation development in the absence of DNA damage

• Autores: Céline Ziegler-Birling, Anne Helmrich, Lászió Tora, María Elena Torres Padilla
• Localización: International journal of developmental biology, ISSN 0214-6282, Vol. 53, Nº. 7, 2009, págs. 1003-1012
• Idioma: inglés
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• Resumen

  • The cells in the preimplantation mammalian embryo undergo several rounds of fast cell division. Whether the known DNA repair pathways are active during these early stages of development where cell division is of primary importance, has not been fully established. Because of the important role of phosphorylated H2A.X (ãH2A.X) in the DNA damage response as well as its putative role in assembly of embryonic chromatin, we analysed its distribution in the preimplantation mouse embryo. We found that H2A.X is highly phosphorylated throughout preimplantation development in the absence of any induced DNA damage. Moreover, ãH2A.X levels vary significantly throughout the cell cycle. Interestingly, after the 4-cell stage, we detected high levels of H2A.X phosphorylation in mitosis, where telomeres appeared focally enriched with ãH2A.X. In contrast, 53BP1, which is known to be recruited to DNA damage sites, is undetectable at mitotic chromosomes at these stages and its localisation changes upon blastocyst formation from mainly nuclear to cytoplasmic. We also show that 53BP1 and ãH2A.X rarely colocalise, suggesting that the high levels of phosphorylation of H2A.X in the embryo might not be directly linked to the DNA damage response in the embryo. Our data suggest that phosphorylation of H2A.X is an important event in the fast dividing cells of the early embryo in the absence of any induced DNA damage. We discuss the possible consequences of these findings on the genomewide chromatin remodelling that ocurs in the preimplantation mammalian embryo.