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Ziegler-Birling, C.* ; Helmrich, A.* ; Tora, L.* ; Torres-Padilla, M.E.*

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

Int. J. Dev. Biol. 53, 1003-1011 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 (gammaH2A.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, gammaH2A.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 gammaH2A.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 gammaH2A.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 genome-wide chromatin remodelling that ocurs in the preimplantation mammalian embryo.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0214-6282
e-ISSN 1696-3547
Journal International Journal of Developmental Biology
Quellenangaben Volume: 53, Issue: 7, Pages: 1003-1011 Article Number: , Supplement: ,
Publisher University of the Basque Country Press (UBC Press)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)