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Replication-independent chromatin loading of Dnmt1 during G2 and M phases

Item Type:Article
Title:Replication-independent chromatin loading of Dnmt1 during G2 and M phases
Creators Name:Easwaran, H.P. and Schermelleh, L. and Leonhardt, H. and Cardoso, M.C.
Abstract:The major DNA methyltransferase, Dnmt1, associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand. In view of the slow kinetics of Dnmt1 in vitro versus the fast progression of the replication fork, we have tested whether Dnmt1 associates with chromatin beyond S phase. Using time-lapse microscopy of mammalian cells expressing green-fluorescent-protein-tagged Dnmt1 and DsRed-tagged DNA Ligase I as a cell cycle progression marker, we have found that Dnmt1 associates with chromatin during G2 and M. This association is mediated by a specific targeting sequence, shows strong preference for constitutive but not facultative heterochromatin and is independent of heterochromatin-specific histone H3 Lys9 trimethylation, SUV39H and HP1. Moreover, photobleaching analyses showed that Dnmt1 is continuously loaded onto chromatin throughout G2 and M, indicating a replication-independent role of Dnmt1 that could represent a novel and separate pathway to maintain DNA methylation.
Keywords:Centromeric Heterochromatin, DNA Methylation, DNA Replication, Dnmt1, Epigenetics, Animals, Mice
Source:EMBO Reports
Publisher:Nature Publishing Group
Page Range:1181-1186
Date:1 January 2004
Official Publication:https://doi.org/10.1038/sj.embor.7400295
PubMed:View item in PubMed

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