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Nat Commun
2022 Aug 23;131:4947. doi: 10.1038/s41467-022-32657-7.
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Nucleosome-directed replication origin licensing independent of a consensus DNA sequence.
Li S
,
Wasserman MR
,
Yurieva O
,
Bai L
,
O'Donnell ME
,
Liu S
.
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The numerous enzymes and cofactors involved in eukaryotic DNA replication are conserved from yeast to human, and the budding yeast Saccharomyces cerevisiae (S.c.) has been a useful model organism for these studies. However, there is a gap in our knowledge of why replication origins in higher eukaryotes do not use a consensus DNA sequence as found in S.c. Using in vitro reconstitution and single-molecule visualization, we show here that S.c. origin recognition complex (ORC) stably binds nucleosomes and that ORC-nucleosome complexes have the intrinsic ability to load the replicative helicase MCM double hexamers onto adjacent nucleosome-free DNA regardless of sequence. Furthermore, we find that Xenopus laevis nucleosomes can substitute for yeast ones in engaging with ORC. Combined with re-analyses of genome-wide ORC binding data, our results lead us to propose that the yeast origin recognition machinery contains the cryptic capacity to bind nucleosomes near a nucleosome-free region and license origins, and that this nucleosome-directed origin licensing paradigm generalizes to all eukaryotes.
Aladjem,
Order from clutter: selective interactions at mammalian replication origins.
2017, Pubmed
Aladjem,
Order from clutter: selective interactions at mammalian replication origins.
2017,
Pubmed
Albert,
Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome.
2007,
Pubmed
Alexiadis,
In vitro chromatin remodelling by chromatin accessibility complex (CHRAC) at the SV40 origin of DNA replication.
1998,
Pubmed
Azmi,
Nucleosomes influence multiple steps during replication initiation.
2017,
Pubmed
Bell,
The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing.
1995,
Pubmed
Bell,
Chromosome Duplication in Saccharomyces cerevisiae.
2016,
Pubmed
Bell,
ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex.
1992,
Pubmed
Bellush,
DNA replication through a chromatin environment.
2017,
Pubmed
Belsky,
Genome-wide chromatin footprinting reveals changes in replication origin architecture induced by pre-RC assembly.
2015,
Pubmed
Bleichert,
Mechanisms for initiating cellular DNA replication.
2017,
Pubmed
Candelli,
Combining optical trapping, fluorescence microscopy and micro-fluidics for single molecule studies of DNA-protein interactions.
2011,
Pubmed
Chang,
High-resolution analysis of four efficient yeast replication origins reveals new insights into the ORC and putative MCM binding elements.
2011,
Pubmed
Cherry,
Saccharomyces Genome Database: the genomics resource of budding yeast.
2012,
Pubmed
Coster,
Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading.
2017,
Pubmed
Crickard,
Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination.
2020,
Pubmed
Das,
MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity.
2014,
Pubmed
De Ioannes,
Structure and function of the Orc1 BAH-nucleosome complex.
2019,
Pubmed
Devbhandari,
Chromatin Constrains the Initiation and Elongation of DNA Replication.
2017,
Pubmed
Duncker,
The origin recognition complex protein family.
2009,
Pubmed
Duzdevich,
The dynamics of eukaryotic replication initiation: origin specificity, licensing, and firing at the single-molecule level.
2015,
Pubmed
Eaton,
Conserved nucleosome positioning defines replication origins.
2010,
Pubmed
Evrin,
A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication.
2009,
Pubmed
,
Xenbase
Ge,
Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress.
2007,
Pubmed
Georgescu,
Mechanism of asymmetric polymerase assembly at the eukaryotic replication fork.
2014,
Pubmed
Gilbert,
In search of the holy replicator.
2004,
Pubmed
Gupta,
A helicase-tethered ORC flip enables bidirectional helicase loading.
2021,
Pubmed
Hizume,
Concerted interaction between origin recognition complex (ORC), nucleosomes and replication origin DNA ensures stable ORC-origin binding.
2013,
Pubmed
Hu,
Evolution of DNA replication origin specification and gene silencing mechanisms.
2020,
Pubmed
Johnson,
Reconstitution of heterochromatin-dependent transcriptional gene silencing.
2009,
Pubmed
Kelly,
Historical Perspective of Eukaryotic DNA Replication.
2017,
Pubmed
Kelly,
Dynamics of DNA replication in a eukaryotic cell.
2019,
Pubmed
Kharerin,
Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.
2021,
Pubmed
Kubik,
Sequence-Directed Action of RSC Remodeler and General Regulatory Factors Modulates +1 Nucleosome Position to Facilitate Transcription.
2018,
Pubmed
Kuo,
The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome.
2012,
Pubmed
Kurat,
Chromatin Controls DNA Replication Origin Selection, Lagging-Strand Synthesis, and Replication Fork Rates.
2017,
Pubmed
Lee,
Humanizing the yeast origin recognition complex.
2021,
Pubmed
Li,
Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors.
2019,
Pubmed
Li,
Structure of the origin recognition complex bound to DNA replication origin.
2018,
Pubmed
Li,
Structure of the eukaryotic MCM complex at 3.8 Å.
2015,
Pubmed
Lockett,
A bacteriophage lambda DNA purification procedure suitable for the analysis of DNA from either large or multiple small lysates.
1990,
Pubmed
Long,
H2A.Z facilitates licensing and activation of early replication origins.
2020,
Pubmed
MacAlpine,
Chromatin and DNA replication.
2013,
Pubmed
Marahrens,
A yeast chromosomal origin of DNA replication defined by multiple functional elements.
1992,
Pubmed
Miller,
Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM.
2019,
Pubmed
Müller,
The conserved bromo-adjacent homology domain of yeast Orc1 functions in the selection of DNA replication origins within chromatin.
2010,
Pubmed
Nieduszynski,
Genome-wide identification of replication origins in yeast by comparative genomics.
2006,
Pubmed
Prioleau,
DNA replication origins-where do we begin?
2016,
Pubmed
Raisner,
Histone variant H2A.Z marks the 5' ends of both active and inactive genes in euchromatin.
2005,
Pubmed
Remus,
Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.
2009,
Pubmed
Rhind,
DNA replication timing.
2013,
Pubmed
Rossi,
A high-resolution protein architecture of the budding yeast genome.
2021,
Pubmed
Sánchez,
DNA replication origins retain mobile licensing proteins.
2021,
Pubmed
Scherr,
Mobile origin-licensing factors confer resistance to conflicts with RNA polymerase.
2022,
Pubmed
Siddiqui,
Regulating DNA replication in eukarya.
2013,
Pubmed
Simpson,
Nucleosome positioning can affect the function of a cis-acting DNA element in vivo.
1990,
Pubmed
Smith,
Chromatin structure and replication origins: determinants of chromosome replication and nuclear organization.
2014,
Pubmed
Speck,
ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA.
2005,
Pubmed
Spivak,
ScerTF: a comprehensive database of benchmarked position weight matrices for Saccharomyces species.
2012,
Pubmed
Stinchcomb,
Isolation and characterisation of a yeast chromosomal replicator.
1979,
Pubmed
Struhl,
Determinants of nucleosome positioning.
2013,
Pubmed
Ticau,
Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading.
2015,
Pubmed
Venditti,
ABFI contributes to the chromatin organization of Saccharomyces cerevisiae ARS1 B-domain.
1994,
Pubmed
Wasserman,
Replication Fork Activation Is Enabled by a Single-Stranded DNA Gate in CMG Helicase.
2019,
Pubmed
Yadon,
Chromatin remodeling around nucleosome-free regions leads to repression of noncoding RNA transcription.
2010,
Pubmed
Yan,
Systematic Study of Nucleosome-Displacing Factors in Budding Yeast.
2018,
Pubmed
Yeeles,
Regulated eukaryotic DNA replication origin firing with purified proteins.
2015,
Pubmed
Yuan,
Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1.
2017,
Pubmed
Zhou,
Genetically encoded short peptide tags for orthogonal protein labeling by Sfp and AcpS phosphopantetheinyl transferases.
2007,
Pubmed