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Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes
Author(s) -
Wossidlo Mark,
Arand Julia,
Sebastiano Vittorio,
Lepikhov Konstantin,
Boiani Michele,
Reinhardt Richard,
Schöler Hans,
Walter Jörn
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.80
Subject(s) - biology , zygote , dna demethylation , dna , genetics , link (geometry) , dna repair , microbiology and biotechnology , dna methylation , gene , embryogenesis , gene expression , computer network , computer science
In mammalian zygotes, the 5‐methyl‐cytosine (5mC) content of paternal chromosomes is rapidly changed by a yet unknown but presumably active enzymatic mechanism. Here, we describe the developmental dynamics and parental asymmetries of DNA methylation in relation to the presence of DNA strand breaks, DNA repair markers and a precise timing of zygotic DNA replication. The analysis shows that distinct pre‐replicative (active) and replicative (active and passive) phases of DNA demethylation can be observed. These phases of DNA demethylation are concomitant with the appearance of DNA strand breaks and DNA repair markers such as γH2A.X and PARP‐1, respectively. The same correlations are found in cloned embryos obtained after somatic cell nuclear transfer. Together, the data suggest that (1) DNA‐methylation reprogramming is more complex and extended as anticipated earlier and (2) the DNA demethylation, particularly the rapid loss of 5mC in paternal DNA, is likely to be linked to DNA repair mechanisms.