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The role of PR-Set7 in replication licensing depends on Suv4-20h.
Genes Dev. 26, 2580-2589 (2012)
PR-Set7 is the sole monomethyltransferase responsible for H4K20 monomethylation (H4K20me1) that is the substrate for further methylation by Suv4-20h1/h2. PR-Set7 is required for proper cell cycle progression and is subject to degradation by the CRL4(Cdt2) ubiquitin ligase complex as a function of the cell cycle and DNA damage. This report demonstrates that PR-Set7 is an important downstream effector of CRL4(Cdt2) function during origin of DNA replication licensing, dependent on Suv4-20h1/2 activity. Aberrant rereplication correlates with decreased levels of H4K20me1 and increased levels of H4K20 trimethylation (H4K20me3). Expression of a degradation-resistant PR-Set7 mutant in the mouse embryo that is normally devoid of Suv4-20 does not compromise development or cell cycle progression unless Suv4-20h is coexpressed. PR-Set7 targeting to an artificial locus results in recruitment of the origin recognition complex (ORC) in a manner dependent on Suv4-20h and H4K20me3. Consistent with this, H4K20 methylation status plays a direct role in recruiting ORC through the binding properties of ORC1 and ORCA/LRWD1. Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes.
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2.362
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Sprache
englisch
Veröffentlichungsjahr
2012
HGF-Berichtsjahr
0
ISSN (print) / ISBN
0890-9369
e-ISSN
1549-5477
Zeitschrift
Genes and Development
Quellenangaben
Band: 26,
Heft: 23,
Seiten: 2580-2589
Verlag
Cold Spring Harbor Laboratory Press
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epigenetics and Stem Cells (IES)
POF Topic(s)
30204 - Cell Programming and Repair
Forschungsfeld(er)
Stem Cell and Neuroscience
PSP-Element(e)
G-506200-001
PubMed ID
23152447
Erfassungsdatum
2012-12-31