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  Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes

Wossidlo, M., Arand, J., Sebastiano, V., Lepikhov, K., Boiani, M., Reinhardt, R., et al. (2010). Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes. EMBO Journal, 29(11), 1877-1888. doi:10.1038/emboj.2010.80.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7ADD-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7ADE-E
Genre: Journal Article

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 Creators:
Wossidlo, Mark, Author
Arand, Julia, Author
Sebastiano, Vittorio, Author
Lepikhov, Konstantin, Author
Boiani, Michele, Author
Reinhardt, Richard1, Author              
Schöler, Hans, Author
Walter, Jörn2, Author              
Affiliations:
1High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433552              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: γH2A.X; DNA demethylation; DNA repair; epigenetic reprogramming; mouse zygote
 Abstract: 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.

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Language(s): eng - English
 Dates: 2010-06-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

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Title: EMBO Journal
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 29 (11) Sequence Number: - Start / End Page: 1877 - 1888 Identifier: ISSN: 0261-4189