Schermelleh, Lothar ; Haemmer, Andrea ; Spada, Fabio ; Rösing, Nicole ; Meilinger, Daniela ; Rothbauer, Ulrich ; Cardoso, M. Cristina ; Leonhardt, Heinrich (2007)
Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.
In: Nucleic acids research, 35 (13)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Postreplicative maintenance of genomic methylation patterns was proposed to depend largely on the binding of DNA methyltransferase 1 (Dnmt1) to PCNA, a core component of the replication machinery. We investigated how the slow and discontinuous DNA methylation could be mechanistically linked with fast and processive DNA replication. Using photobleaching and quantitative live cell imaging we show that Dnmt1 binding to PCNA is highly dynamic. Activity measurements of a PCNA-binding-deficient mutant with an enzyme-trapping assay in living cells showed that this interaction accounts for a 2-fold increase in methylation efficiency. Expression of this mutant in mouse dnmt1-/- embryonic stem (ES) cells restored CpG island methylation. Thus association of Dnmt1 with the replication machinery enhances methylation efficiency, but is not strictly required for maintaining global methylation. The transient nature of this interaction accommodates the different kinetics of DNA replication and methylation while contributing to faithful propagation of epigenetic information.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2007 |
| Autor(en): | Schermelleh, Lothar ; Haemmer, Andrea ; Spada, Fabio ; Rösing, Nicole ; Meilinger, Daniela ; Rothbauer, Ulrich ; Cardoso, M. Cristina ; Leonhardt, Heinrich |
| Art des Eintrags: | Bibliographie |
| Titel: | Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. |
| Sprache: | Englisch |
| Publikationsjahr: | 2007 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nucleic acids research |
| Jahrgang/Volume einer Zeitschrift: | 35 |
| (Heft-)Nummer: | 13 |
| URL / URN: | http://www.cardoso-lab.org/publications/Schermelleh_et_al_20... |
| Kurzbeschreibung (Abstract): | Postreplicative maintenance of genomic methylation patterns was proposed to depend largely on the binding of DNA methyltransferase 1 (Dnmt1) to PCNA, a core component of the replication machinery. We investigated how the slow and discontinuous DNA methylation could be mechanistically linked with fast and processive DNA replication. Using photobleaching and quantitative live cell imaging we show that Dnmt1 binding to PCNA is highly dynamic. Activity measurements of a PCNA-binding-deficient mutant with an enzyme-trapping assay in living cells showed that this interaction accounts for a 2-fold increase in methylation efficiency. Expression of this mutant in mouse dnmt1-/- embryonic stem (ES) cells restored CpG island methylation. Thus association of Dnmt1 with the replication machinery enhances methylation efficiency, but is not strictly required for maintaining global methylation. The transient nature of this interaction accommodates the different kinetics of DNA replication and methylation while contributing to faithful propagation of epigenetic information. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie > Cell Biology and Epigenetics ?? fb10_zoologie ?? 10 Fachbereich Biologie |
| Hinterlegungsdatum: | 06 Mär 2010 15:45 |
| Letzte Änderung: | 05 Mär 2013 09:32 |
| PPN: | |
| Export: | |
| Suche nach Titel in: | TUfind oder in Google |
 |
Frage zum Eintrag |
Optionen (nur für Redakteure)
 |
Redaktionelle Details anzeigen |
Drucken
Impressum