SubunitBudding yeastProteinsORC1SaccharomycesORC2Eukaryotic DNA replication oriNucleic acidCdc6 and Cdt1Yeast origin recogniNuclearBoundSister chromatid cohesionORCsCyclinBindsChromosomalProtein complexCdt1StructuresInitiationEnrichmentCerevisiaeNucleusStillman2017Nucleosome organizationHelicase complexSpeciesPutativeInitiatorPhaseGenomeARS1LocalizationAnnotationsMethyltransferasesMacromolecularDefinesEukaryotesPhosphorylationSIR3ReplicativeMechanismsCell
Subunit3
- In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes and archaea in an ATP-dependent manner to origins of replication. (wikipedia.org)
- A global analysis of DNA replication initiation in T. brucei showed that TbORC1 (subunit of the origin recognition complex, ORC) binding sites are located at the boundaries of transcription units. (umass.edu)
- The six subunit Origin Recognition Complex (ORC) together with Cdc6 and Cdt1, load the MCM replicative helicase as a double hexamer around double stranded DNA at origins. (crick.ac.uk)
Budding yeast2
- A highly conserved sequence of 11bp (known as the A element) is thought to be essential for origin function in budding yeast. (wikipedia.org)
- Here, using genome-scale biochemical reconstitution with approximately 300 replication origins, we screened 17 purified chromatin factors from budding yeast and found that the ORC established nucleosome depletion over replication origins and flanking nucleosome arrays by orchestrating the chromatin remodellers INO80, ISW1a, ISW2 and Chd1. (nature.com)
Proteins12
- To better understand how cells regulate and initiate replication of their genomes, Berger and his colleagues are studying origin-binding proteins, helicases, primases and accessory remodeling factors from a variety of organisms within the three cellular domains of life. (hopkinsmedicine.org)
- DNA replication origins retain mobile licensing proteins. (yeastgenome.org)
- The origin recognition complex (ORC) is a group of proteins involved with every cell division event in our cells. (cshl.edu)
- The ORC complex proteins are kept near each other in liquid compartments in the nucleus and recruit proteins such as CDC6 and other proteins that control when to commit the cell to divide. (cshl.edu)
- Increasingly, biologists are investigating large molecules made up of combinations of RNA and proteins, called RNA-protein complexes. (nih.gov)
- In cell cultures, through RNA affinity purification, a process that isolates a single type of protein from a complex mixture, the team identified telomeric proteins (Shelterin components TRF1 and TRF2, and origin recognition complex subunits ORC1, ORC2, and ORC4) that bound to a TERRA oligonucleotide sequence but not to control oligonucleotides. (news-medical.net)
- Using RNA chromatin immunoprecipitation assays (ChIPs), in which specific pieces of RNA are isolated from bound proteins, the team discovered that TERRA is bound by telomeric proteins indicating that TERRA was a component of the Shelterin complex. (news-medical.net)
- Later, in the S phase of the cell cycle, other proteins assemble onto the complex, converting the Mcm2-7 hexamers into helicases that unwind the DNA for replication ( Figure 1D ). (elifesciences.org)
- studied how three proteins - ORC (green), Cdt1 (purple) and Cdc6 (blue) - work together to help two Mcm2-7 hexamers (yellow) form a pre-replicative complex with DNA (red). (elifesciences.org)
- Dhar, S.K . Functional characterization of replication origin ( oric ) & replication proteins of Helicobacter pylori . (jnu.ac.in)
- The authors identified proteins associated with the yeast origin recognition complex (ORC), a set of proteins that binds chromosomal origins of DNA replication. (rupress.org)
- Yph1p was also found in complex with a variety of other proteins, including those involved in ribosome biogenesis, cell cycle regulation, and checkpoint control. (rupress.org)
ORC12
- ORC1 interacts with ATP and these basic residues in order to bind the ORC to origin DNA. (wikipedia.org)
- Fig. 3: Effects of Orc1 mutations on cell viability, complex formation, origin DNA binding and MCM loading. (nature.com)
Saccharomyces3
- Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae. (yeastgenome.org)
- The origin recognition complex (ORC) was originally identified in the yeast Saccharomyces cerevisiae as a protein that specifically binds to origins of DNA replication. (embl.de)
- In analyzing the stability of DNA replication origins in Saccharomyces cerevisiae we faced the question whether one set of sequences is significantly enriched in the number and/or the quality of the matches of a particular position weight matrix relative to another set. (biomedcentral.com)
ORC23
- Interactions within ORC suggest that Orc2-3-6 may form a core complex. (wikipedia.org)
- We have identified origin recognition complex 2 (Orc2), a member of the DNA replication machinery, as a Plk1 substrate and have shown that Plk1 phosphorylates Orc2 at Ser188 in vitro and in vivo. (uky.edu)
- To dissect the mechanism pertinent to this observation, we showed that Orc2-S188 phosphorylation associates with DNA replication origin and that cells expressing Orc2-S188A mutant fail to maintain the functional pre-replicative complex (pre-RC) under DNA replication stress. (uky.edu)
Eukaryotic DNA replication ori1
- Berbenetz, N. M., Nislow, C. & Brown, G. W. Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure. (nature.com)
Nucleic acid1
- The approach relies on a blend of structural, biochemical, and biophysical methods to define the architecture, function, evolution, and regulation of protein/nucleic acid complexes. (hopkinsmedicine.org)
Cdc6 and Cdt11
- B ) During the G1 phase of the cell cycle intrinsically disordered regions (IDR) in the origin of replication complex (ORC), Cdc6 and Cdt1 bind a DNA molecule to form a biomolecular condensate. (elifesciences.org)
Yeast origin recogni1
- Architecture of the yeast origin recognition complex bound to origins of DNA replication. (harvard.edu)
Nuclear2
- Journal Article] Compositionally distinct nuclear pore complexes of functionally distinct dimorphic nuclei in ciliate Tetrahymena. (nii.ac.jp)
- Cdt1p, through its interaction with Mcm6p, is required for the formation, nuclear accumulation and chromatin loading of the MCM complex. (yeastgenome.org)
Bound5
- ORC is a central component for eukaryotic DNA replication, and remains bound to chromatin at replication origins throughout the cell cycle. (wikipedia.org)
- ORC and Noc3p bound at replication origins serve as the foundation for assembly of the pre-replication complex (pre-RC), which includes Cdc6, Tah11 (a.k.a. (wikipedia.org)
- The ORC is present throughout the cell cycle bound to replication origins, but is only active in late mitosis and early G1. (wikipedia.org)
- It has been established that this occurs far before replication, and that the ORC itself is already bound to Origin DNA by the time any Mcm2-7 loading occurs. (wikipedia.org)
- Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC-Cdc6 bound to an 85-bp ARS1 origin DNA. (imperial.ac.uk)
Sister chromatid cohesion1
- Functional control of Eco1 through the MCM complex in sister chromatid cohesion. (yeastgenome.org)
ORCs2
- Origin recognition complexes (ORCs) initiate the task of DNA replication throughout an entire genome in a controlled, temporal pattern. (cshl.edu)
- The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
Cyclin1
- cdc2 protein kinase is complexed with both cyclin A and B: Evidence for proteolytic inactivation of MPF. (cshlpress.com)
Binds2
- The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. (imperial.ac.uk)
- The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks. (embl.de)
Chromosomal1
- DNA replication in eukaryotic cells initiates from a large number of chromosomal sites known as origins. (crick.ac.uk)
Protein complex2
- As originally proposed in 1963, cells rely on two genetic elements to duplicate their genome: the replicator, a DNA region where replication begins (now named the replication origin), and the initiator, a protein or a protein complex that recognizes the replicator [ 1 ]. (biomedcentral.com)
- The MCM2-7 protein complex is the precursor of the replicative helicase that unwinds DNA in front of the active replication complex. (biomedcentral.com)
Cdt15
- Cdt1), and the Mcm2-Mcm7 complex. (wikipedia.org)
- Sulfolobus islandicus also uses a Cdt1 homologue to recognize one of its replication origins. (wikipedia.org)
- New ORC/Noc3/Cdc6 complexes then recruit Cdt1/Mcm2-7 molecules to the site. (wikipedia.org)
- Once this massive ORC/Noc3/Cdc6/Cdt1/Mcm2-7 complex is formed, the ORC/Noc3/Cdc6/Cdt1 molecules work together to load Mcm2-7 onto the DNA itself by hydrolysis of ATP by Cdc6. (wikipedia.org)
- This leads to Cdt1 having decreased stability on the DNA and falling off of the complex leading to Mcm2-7 loading on to the DNA. (wikipedia.org)
Structures5
- In fact, they have divergent complex structures when these do form. (wikipedia.org)
- Dr. Berger's team has solved structures of topoisomerase targets in complex with target DNA substrates and various drugs. (hopkinsmedicine.org)
- However, the replisome can be stalled by depletion of nucleotide pools or barriers on the template, such as DNA damage, secondary structures or protein complexes [ 11 ]. (biomedcentral.com)
- This shift has been made possible in part by a growing number of solved protein structures, often in complex with DNA, and elegant single-molecule approaches. (biomedcentral.com)
- Michael Botchan (University of California, Berkeley, USA) presented three-dimensional electron microscopy structures of the entire Drosophila melanogaster CMG complex. (biomedcentral.com)
Initiation1
- The origin recognition complex (ORC) is essential for initiation of eukaryotic chromosome replication as it loads the replicative helicase-the minichromosome maintenance (MCM) complex-at replication origins 1 . (nature.com)
Enrichment1
- The putative origins identified in T. cruzi show a notable enrichment of GC content, a preferential position at subtelomeric regions, coinciding with genes transcribed towards the telomeres, and a pronounced enrichment within coding DNA sequences, most notably in genes from the Dispersed Gene Family 1 (DGF-1). (biomedcentral.com)
Cerevisiae1
- In analyzing the stability of DNA replication origins in S. cerevisiae (see Stable vs. unstable ARSs in mcm1-1 mutant below) we faced the question of whether one set of sequences has more and/or better binding sites of a particular transcription factor than the other. (biomedcentral.com)
Nucleus1
- A cartoon of a section of chromatin in the nucleus with replication origins in three different states. (crick.ac.uk)
Stillman2
- A protein found in DNA replication complexes is also essential for ribosome biosynthesis, according to new results from Yi-Chieh Du and Bruce Stillman (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). (rupress.org)
- The first link to ribosome biosynthesis came from the finding of Erb1p in the Yph1p complex," says Stillman. (rupress.org)
20171
- In recognition of Rare Disease Day 2017 , we republish, with permission, a modified extract from our recent commentary in Genetics in Medicine. (cdc.gov)
Nucleosome organization2
- Our results establish that ORC, in addition to its canonical role as the MCM loader, has a second crucial function as a master regulator of nucleosome organization at the replication origin, a crucial prerequisite for efficient chromosome replication. (nature.com)
- Fig. 1: ORC is a master regulator of nucleosome organization at origins of replication. (nature.com)
Helicase complex1
- For the future, a more detailed understanding of the paths of the leading and lagging DNA strands running through the CMG helicase complex towards the DNA polymerases is needed. (biomedcentral.com)
Species1
- Identifying conserved protein complexes between species by constructing interolog networks. (yeastgenome.org)
Putative2
- These findings suggest a scenario where collisions between DNA replication and transcription are frequent, leading to increased genetic variability, as seen by the increase SNP levels at chromosome subtelomeres and in DGF-1 genes containing putative origins. (biomedcentral.com)
- Programme Support on Molecular Parasitology" to work on the project entitled "Characterization of DNA replication and non-replication function of two putative homologues of Plasmodium falciparum Origin Recognition Complex" Department of Biotechnology (DBT) (2011-2016). (jnu.ac.in)
Initiator2
- The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. (imperial.ac.uk)
- Taken together, considerably greater flexibility in initiator-directed origin usage is found in eukaryotes than in prokaryotes. (biomedcentral.com)
Phase2
- Then, when cells reach S-phase, a set of enzymatic and regulatory factors activate some, but not all, origins, which are differently used depending on the cell types and stages of development, and even in different cells of the same population. (biomedcentral.com)
- This occurs in vivo during G1 phase and remains until origin firing during S phase. (crick.ac.uk)
Genome2
- Nieduszynski, C. A., Knox, Y. & Donaldson, A. D. Genome-wide identification of replication origins in yeast by comparative genomics. (nature.com)
- The human Mre11/Rad50 complex is one of the key factors in genome maintenance pathways. (bvsalud.org)
ARS11
- pombe replication origin, ars1. (embl.de)
Localization1
- Localization and sequence analysis of yeast origins of DNA replication. (nature.com)
Annotations1
- Macromolecular complex annotations are imported from the Complex Portal . (yeastgenome.org)
Methyltransferases1
- 1) Various complex formation of Histone methyltransferases for repressive chromatin and the molecular basis of their formation, 2) Relationship between heterochromatin formation and repressive histone modification on inactive X chromosome, 3) Involvement of an HP1 binding protein in pathway choice for repairing double-strand breaks. (nii.ac.jp)
Macromolecular1
- Work from their group is revealing important information about the mechanisms of origin processing, primer synthesis, and macromolecular assembly that occur during replisome construction. (hopkinsmedicine.org)
Defines1
- The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif. (embl.de)
Eukaryotes1
- In all other eukaryotes, clear consensus sequences for origins are elusive, perhaps indicating there are no cis elements to initiate replication in most of these cells and organisms. (biomedcentral.com)
Phosphorylation1
- Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex. (yeastgenome.org)
SIR31
- Yeast heterochromatin regulators Sir2 and Sir3 act directly at euchromatic DNA replication origins. (yeastgenome.org)
Replicative1
- C ) The biomolecular condensate forms a scaffold that the Mcm2-7 hexamer can enter, and the pre-replicative complex is formed. (elifesciences.org)
Mechanisms1
- Researchers have visualized the structure of this complex, dissected its mechanisms in starting DNA replication, and discovered other roles the ORC plays. (cshl.edu)
Cell1
- The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)