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Recruitment of DNA methyltransferase I to DNA repair sites.

Mortusewicz, Oliver and Schermelleh, Lothar and Walter, Joachim and Cardoso, M Cristina and Leonhardt, Heinrich (2005):
Recruitment of DNA methyltransferase I to DNA repair sites.
In: Proceedings of the National Academy of Sciences of the United States of America, pp. 8905-9, 102, (25), ISSN 0027-8424,
[Online-Edition: http://www.cardoso-lab.org/publications/Mortusewicz_2005.pdf],
[Article]

Abstract

In mammalian cells, the replication of genetic and epigenetic information is directly coupled; however, little is known about the maintenance of epigenetic information in DNA repair. Using a laser microirradiation system to introduce DNA lesions at defined subnuclear sites, we tested whether the major DNA methyltransferase (Dnmt1) or one of the two de novo methyltransferases (Dnmt3a, Dnmt3b) are recruited to sites of DNA repair in vivo. Time lapse microscopy of microirradiated mammalian cells expressing GFP-tagged Dnmt1, Dnmt3a, or Dnmt3b1 together with red fluorescent protein-tagged proliferating cell nuclear antigen (PCNA) revealed that Dnmt1 and PCNA accumulate at DNA damage sites as early as 1 min after irradiation in S and non-S phase cells, whereas recruitment of Dnmt3a and Dnmt3b was not observed. Deletion analysis showed that Dnmt1 recruitment was mediated by the PCNA-binding domain. These data point to a direct role of Dnmt1 in the restoration of epigenetic information during DNA repair.

Item Type: Article
Erschienen: 2005
Creators: Mortusewicz, Oliver and Schermelleh, Lothar and Walter, Joachim and Cardoso, M Cristina and Leonhardt, Heinrich
Title: Recruitment of DNA methyltransferase I to DNA repair sites.
Language: German
Abstract:

In mammalian cells, the replication of genetic and epigenetic information is directly coupled; however, little is known about the maintenance of epigenetic information in DNA repair. Using a laser microirradiation system to introduce DNA lesions at defined subnuclear sites, we tested whether the major DNA methyltransferase (Dnmt1) or one of the two de novo methyltransferases (Dnmt3a, Dnmt3b) are recruited to sites of DNA repair in vivo. Time lapse microscopy of microirradiated mammalian cells expressing GFP-tagged Dnmt1, Dnmt3a, or Dnmt3b1 together with red fluorescent protein-tagged proliferating cell nuclear antigen (PCNA) revealed that Dnmt1 and PCNA accumulate at DNA damage sites as early as 1 min after irradiation in S and non-S phase cells, whereas recruitment of Dnmt3a and Dnmt3b was not observed. Deletion analysis showed that Dnmt1 recruitment was mediated by the PCNA-binding domain. These data point to a direct role of Dnmt1 in the restoration of epigenetic information during DNA repair.

Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 102
Number: 25
Divisions: 10 Department of Biology > Cell Biology and Epigenetics
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10 Department of Biology
Date Deposited: 06 Mar 2010 07:46
Official URL: http://www.cardoso-lab.org/publications/Mortusewicz_2005.pdf
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