Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Structure and function of the Orc1 BAH-nucleosome complex

Journal Article · · Nature Communications
 [1];  [2];  [3];  [4];  [5];  [2];  [4]
  1. New York Univ. (NYU), NY (United States). School of Medicine; DOE/OSTI
  2. New York Univ. (NYU), NY (United States)
  3. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); New York University (NYU) Langone Health, NY (United States)
  4. New York Univ. (NYU), NY (United States). School of Medicine
  5. New York University (NYU) Langone Health, NY (United States)
The Origin Recognition Complex (ORC) is essential for replication, heterochromatin formation, telomere maintenance and genome stability in eukaryotes. Here we present the structure of the yeast Orc1 BAH domain bound to the nucleosome core particle. Our data reveal that Orc1, unlike its close homolog Sir3 involved in gene silencing, does not appear to discriminate between acetylated and non-acetylated lysine 16, modification states of the histone H4 tail that specify open and closed chromatin respectively. We elucidate the mechanism for this unique feature of Orc1 and hypothesize that its ability to interact with nucleosomes regardless of K16 modification state enables it to perform critical functions in both hetero- and euchromatin. We also show that direct interactions with nucleosomes are essential for Orc1 to maintain the integrity of rDNA borders during meiosis, a process distinct and independent from its known roles in silencing and replication.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
David and Lucile Packard Foundation; NYU School of Medicine; National Institutes of Health (NIH); USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1562715
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

References (79)

A yeast silencer contains sequences that can promote autonomous plasmid replication and transcriptional activation journal December 1987
The multidomain structure of Orc1 p reveals similarity to regulators of DNA replication and transcriptional silencing journal November 1995
Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: A molecular model for the formation of heterochromatin in yeast journal February 1995
Quantitative Interaction Proteomics and Genome-wide Profiling of Epigenetic Histone Marks and Their Readers journal September 2010
Mapping of Meiotic Single-Stranded DNA Reveals Double-Strand-Break Hotspots near Centromeres and Telomeres journal December 2007
Crystal Structures of Nucleosome Core Particles Containing the ‘601’ Strong Positioning Sequence journal October 2010
Role of the Conserved Sir3-BAH Domain in Nucleosome Binding and Silent Chromatin Assembly journal December 2007
Reconstitution of Yeast Silent Chromatin: Multiple Contact Sites and O-AADPR Binding Load SIR Complexes onto Nucleosomes In Vitro journal February 2009
High-Resolution Chromatin Dynamics during a Yeast Stress Response journal April 2015
Greater Than the Sum of Parts: Complexity of the Dynamic Epigenome journal June 2016
The BAH (bromo-adjacent homology) domain: a link between DNA methylation, replication and transcriptional regulation journal March 1999
Chromatin Fiber Folding: Requirement for the Histone H4 N-terminal Tail journal March 2003
Genetically Encoding Lysine Modifications on Histone H4 journal January 2015
ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex journal May 1992
Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing journal May 1996
Crystal structure of the nucleosome core particle at 2.8 Å resolution journal September 1997
A dual role of H4K16 acetylation in the establishment of yeast silent chromatin: Dual role of H4K16 journal June 2011
Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae journal March 2004
Protection of repetitive DNA borders from self-induced meiotic instability journal August 2011
Crystal structure of the eukaryotic origin recognition complex journal March 2015
Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin journal October 2002
Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing journal October 2002
Nα-acetylated Sir3 stabilizes the conformation of a nucleosome-binding loop in the BAH domain journal August 2013
Transcriptional silencing functions of the yeast protein Orc1/Sir3 subfunctionalized after gene duplication journal October 2010
Heterochromatin protein Sir3 induces contacts between the amino terminus of histone H4 and nucleosomal DNA journal May 2013
Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing journal September 2002
Two Classes of sir3 Mutants Enhance the sir1 Mutant Mating Defect and Abolish Telomeric Silencing in Saccharomyces cerevisiae journal June 2000
The role of the nucleosome acidic patch in modulating higher order chromatin structure journal May 2013
Epigenetics in Saccharomyces cerevisiae journal July 2013
Silent information regulator 3: the Goldilocks of the silencing complex journal January 2010
The role of PR-Set7 in replication licensing depends on Suv4-20h journal November 2012
The molecular topography of silenced chromatin in Saccharomyces cerevisiae journal February 2014
Genome-wide chromatin footprinting reveals changes in replication origin architecture induced by pre-RC assembly journal January 2015
The origin recognition complex: from simple origins to complex functions journal March 2002
Acetylation of Yeast Histone H4 Lysine 16: A Switch for Protein Interactions in Heterochromatin and Euchromatin journal January 2004
Phaser crystallographic software journal July 2007
Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions journal February 2006
Structural Basis of Silencing: Sir3 BAH Domain in Complex with a Nucleosome at 3.0 A Resolution journal November 2011
The Origin Recognition Complex, SIR1, and the S Phase Requirement for Silencing journal June 1997
Roles for ORC in M Phase and S Phase journal March 1998
Yeast origin recognition complex functions in transcription silencing and DNA replication journal December 1993
Expanded Roles of the Origin Recognition Complex in the Architecture and Function of Silenced Chromatin in Saccharomyces cerevisiae journal November 2009
Sir3-Nucleosome Interactions in Spreading of Silent Chromatin in Saccharomyces cerevisiae journal September 2008
Notes: Point Mutations in the Yeast Histone H4 Gene Prevent Silencing of the Silent Mating Type Locus HML journal September 1990
Dependence of ORC Silencing Function on NatA-Mediated N  Acetylation in Saccharomyces cerevisiae journal November 2004
Structure and Function of the Saccharomyces cerevisiae Sir3 BAH Domain journal March 2006
Self-Organization of Meiotic Recombination Initiation: General Principles and Molecular Pathways journal November 2014
The origin recognition complex protein family journal January 2009
Compensatory Interactions between Sir3p and the Nucleosomal LRS Surface Imply Their Direct Interaction journal December 2008
Dissecting Nucleosome Function with a Comprehensive Histone H2A and H2B Mutant Library journal October 2017
Structure and function of the BAH domain in chromatin biology journal November 2012
Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: A molecular model for the formation of heterochromatin in yeast journal February 1995
The BAH (bromo-adjacent homology) domain: a link between DNA methylation, replication and transcriptional regulation journal March 1999
Chromatin Fiber Folding: Requirement for the Histone H4 N-terminal Tail journal March 2003
Preparation of nucleosome core particle from recombinant histones book January 1999
The Single-End Invasion journal July 2001
The molecular biology of the SIR proteins journal November 2001
A Method for Genetically Installing Site-Specific Acetylation in Recombinant Histones Defines the Effects of H3 K56 Acetylation journal October 2009
Reconstitution of Heterochromatin-Dependent Transcriptional Gene Silencing journal September 2009
Recognition of the nucleosome by chromatin factors and enzymes journal April 2016
The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier–Gorlin syndrome journal March 2012
The N-terminal acetylation of Sir3 stabilizes its binding to the nucleosome core particle journal August 2013
Structural basis of the Sir1-origin recognition complex interaction in transcriptional silencing journal June 2005
Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae. journal August 1990
Genetic Analysis of Rap1p/Sir3p Interactions in Telomeric and HML Silencing in Saccharomyces cerevisiae journal May 1996
The conserved bromo-adjacent homology domain of yeast Orc1 functions in the selection of DNA replication origins within chromatin journal July 2010
Conserved nucleosome positioning defines replication origins journal March 2010
Histone H4 and the maintenance of genome integrity. journal July 1995
Phaser crystallographic software journal July 2007
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Features and development of Coot journal March 2010
Expanded Roles of the Origin Recognition Complex in the Architecture and Function of Silenced Chromatin in Saccharomyces cerevisiae journal November 2009
Sir3-Nucleosome Interactions in Spreading of Silent Chromatin in Saccharomyces cerevisiae journal September 2008
Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML. journal September 1990
Dependence of ORC Silencing Function on NatA-Mediated N  Acetylation in Saccharomyces cerevisiae journal November 2004
Structure and Function of the Saccharomyces cerevisiae Sir3 BAH Domain journal March 2006
SIR Proteins and the Assembly of Silent Chromatin in Budding Yeast journal November 2013
Importance of the Sir3 N Terminus and Its Acetylation for Yeast Transcriptional Silencing journal September 2004
Chromosome Duplication in Saccharomyces cerevisiae journal July 2016

Similar Records

The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome
Journal Article · Wed Jul 11 00:00:00 EDT 2012 · Nature · OSTI ID:1039777

Structural Basis of Silencing: Sir3 BAH Domain in Complex with a Nucleosome at 3.0 Å Resolution
Journal Article · Tue Nov 29 23:00:00 EST 2011 · Science (Washington, D.C.) · OSTI ID:1030438

Structure and Function of the Saccharomyces Cerevisiae Sir3 BAH Domain
Journal Article · Sat Dec 31 23:00:00 EST 2005 · Molecular and Cellular Biology · OSTI ID:930572