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

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 Lys 9 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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Easwaran HP,Schermelleh L,Leonhardt H,Cardoso MC

doi

10.1038/sj.embor.7400295

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

1181-6

issue

12

eissn

1469-221X

issn

1469-3178

pii

7400295

journal_volume

5

pub_type

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