Document Detail

A WD-repeat protein stabilizes ORC binding to chromatin.
MedLine Citation:
PMID:  20932478     Owner:  NLM     Status:  MEDLINE    
Origin recognition complex (ORC) plays critical roles in the initiation of DNA replication and cell-cycle progression. In metazoans, ORC associates with origin DNA during G1 and with heterochromatin in postreplicated cells. However, what regulates the binding of ORC to chromatin is not understood. We have identified a highly conserved, leucine-rich repeats and WD40 repeat domain-containing protein 1 (LRWD1) or ORC-associated (ORCA) in human cells that interacts with ORC and modulates chromatin association of ORC. ORCA colocalizes with ORC and shows similar cell-cycle dynamics. We demonstrate that ORCA efficiently recruits ORC to chromatin. Depletion of ORCA in human primary cells and embryonic stem cells results in loss of ORC association to chromatin, concomitant reduction of MCM binding, and a subsequent accumulation in G1 phase. Our results suggest ORCA-mediated association of ORC to chromatin is critical to initiate preRC assembly in G1 and chromatin organization in post-G1 cells.
Zhen Shen; Kizhakke M Sathyan; Yijie Geng; Ruiping Zheng; Arindam Chakraborty; Brian Freeman; Fei Wang; Kannanganattu V Prasanth; Supriya G Prasanth
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Molecular cell     Volume:  40     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-11     Completed Date:  2010-11-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  99-111     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, IL 61801, USA.
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MeSH Terms
Adaptor Proteins, Signal Transducing / genetics,  metabolism*
Amino Acid Sequence
Binding Sites
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Chromatin Assembly and Disassembly*
Conserved Sequence
Fluorescent Antibody Technique
Heterochromatin / metabolism*
Microscopy, Video
Molecular Sequence Data
Origin Recognition Complex / genetics,  metabolism*
Protein Binding
Protein Interaction Domains and Motifs
RNA Interference
Recombinant Fusion Proteins / metabolism
Time Factors
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Heterochromatin; 0/Origin Recognition Complex; 0/Recombinant Fusion Proteins; 0/SQSTM1 protein, human

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