Document Detail

The role of PR-Set7 in replication licensing depends on Suv4-20h.
MedLine Citation:
PMID:  23152447     Owner:  NLM     Status:  MEDLINE    
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.
David B Beck; Adam Burton; Hisanobu Oda; Céline Ziegler-Birling; Maria-Elena Torres-Padilla; Danny Reinberg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-04     Completed Date:  2013-01-25     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2580-9     Citation Subset:  IM    
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MeSH Terms
Cell Cycle / genetics,  physiology*
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
DNA Damage
DNA Replication / genetics,  physiology*
Embryo, Mammalian
Fibroblasts / cytology
HeLa Cells
Histone-Lysine N-Methyltransferase / genetics,  metabolism*
Origin Recognition Complex / metabolism
Protein Binding
Ubiquitin-Protein Ligases / metabolism
Grant Support
GM64844/GM/NIGMS NIH HHS; R01 GM064844/GM/NIGMS NIH HHS; T32 GM007308/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Origin Recognition Complex; EC protein, mouse; EC N-Methyltransferase; EC protein, human; EC Ligases

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