Origin recognition complex subunit 1 (ORC1) is the 120 kDa catalytic subunit of the ORC complex, essential for DNA replication initiation and mating-type transcriptional silencing. ORC1 recognizes and binds ARS consensus sequences at replication origins, recruits MCM2-7 loading factors during G1, and interacts with SIR proteins to establish heterochromatin at silent mating loci. The protein contains an N-terminal BAH (bromo-adjacent homology) domain for nucleosome binding and a C-terminal AAA+ ATPase domain for ATP-dependent chromatin remodeling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006270 DNA replication initiation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation well-supported by experimental evidence and phylogenetic orthology. ORC1 is essential for G1/S loading of MCM complexes and formation of the pre-replicative complex. Reason: Core function. Multiple experimental studies (IDA, IMP, NAS) confirm ORC1s role in DNA replication initiation through pre-replicative complex assembly and MCM loading. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md In early G1, ORC (including Orc1) recruits **Cdc6**, then **Cdt1–MCM2–7**, loading MCM one hexamer at a time to form a head-to-head MCM double hexamer |
| GO:0003688 DNA replication origin binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation reflects the fundamental mechanism by which ORC1 initiates DNA replication through recognition of ARS consensus sequences. Reason: Core molecular function. ORC1 specifically binds ARS consensus sequences (ACS) at replication origins. This is well-established experimentally (IDA evidence PMID:16824194). Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md recognizes a replication-origin DNA consensus (ARS consensus sequence, ACS) and acts as the platform that seeds helicase loading and replication initiation |
| GO:0033314 mitotic DNA replication checkpoint signaling | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA annotation inferred from phylogenetic orthology. ORC1 is involved in checkpoint responses to aberrant replication. Reason: While ORC1 is involved in replication checkpoint signaling, this is peripheral to its primary role in replication initiation. The checkpoint function is largely indirect through replication failure surveillance. IBA annotations are conservative and this may represent a non-essential secondary function. Supporting Evidence: PMID:16716188 Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae |
| GO:0005664 nuclear origin of replication recognition complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly identifies ORC1 as part of the ORC complex, a multi-subunit assembly. Reason: Accurate. ORC1 is a core structural component of the ORC complex. Experimentally validated (IDA, IMP evidence). Supporting Evidence: PMID:9372948 Architecture of the yeast origin recognition complex bound to origins of DNA replication file:yeast/ORC1/ORC1-deep-research-falcon.md ORC is a large (~400 kDa) heterohexamer (Orc1–6) that recognizes a replication-origin DNA consensus |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation based on UniProtKB keyword mapping. ORC1 contains AAA+ ATPase domain with ATP binding capability. Reason: Mechanically correct but overly generic. ORC1 contains multiple ATP binding sites (documented in UniProt features), but the more specific ATP binding annotation (GO:0005524) is more informative. Nucleotide binding as a general term lacks specificity for ORC1s characterized ATP hydrolysis activity. Supporting Evidence: file:yeast/ORC1/ORC1-deep-research-falcon.md ATP binding by Orc1 is required for ORC DNA binding |
| GO:0003677 DNA binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation based on UniProtKB keyword mapping reflects ORC1s well-documented ARS-binding capability. Reason: Technically accurate but too generic. GO:0003688 (DNA replication origin binding) is more specific and informative. General DNA binding term obscures the specialized function of recognizing specific ARS sequences. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 and Orc2 contribute **minor-groove interactions** (e.g., Orc1 basic patch) |
| GO:0003682 chromatin binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation inferred from InterPro BAH domain (IPR001025). ORC1 contains a BAH domain for nucleosome interaction. Reason: Mechanically correct - ORC1 has a BAH domain and binds chromatin/nucleosomes. The more specific nucleosome binding term (GO:0031491) is also annotated with IDA evidence, so this broader term is acceptable as a complementary annotation. Supporting Evidence: PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex file:yeast/ORC1/ORC1-deep-research-falcon.md The N-terminal BAH domain of Orc1 is a chromatin-binding module distinct from the AAA+ region |
| GO:0003688 DNA replication origin binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA machine learning model correctly identifies ORC1s origin binding function. Reason: Well-supported. This duplicates the IBA and IDA annotations for the same term but with different evidence code. Core molecular function. Experimental validation exists (IDA PMID:16824194). Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated methods identifies ATP binding in AAA+ domain. Reason: Mechanically correct - ORC1 has well-documented ATP binding sites (see UniProt features at positions 435, 479-487, 567, 600, 704, 726-733). While ATP hydrolysis activity is also annotated, ATP binding is a distinct and essential molecular function. Supporting Evidence: file:yeast/ORC1/ORC1-deep-research-falcon.md ATP binding by Orc1 is required for ORC DNA binding |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA annotation from UniProtKB subcellular location vocabulary correctly identifies nuclear localization. Reason: Correct but non-specific cellular component term. ORC1 is nuclear, but this is required for all its functions. Experimental evidence (EXP, IDA) for nucleoplasm and nucleus localization available. Supporting Evidence: PMID:11168584 Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae |
| GO:0005694 chromosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation from ARBA model identifies ORC1s chromosomal localization during S phase. Reason: Correct but redundant with nucleus/nucleoplasm annotations. ORC1 binds chromosomal DNA at replication origins, but this is implicit in its origin binding function. Not a distinct function, rather a cellular location consequence. |
| GO:0006260 DNA replication | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation based on UniProtKB keyword mapping reflects ORC1s essential role in DNA replication process. Reason: Core biological process. ORC1 is essential for DNA replication initiation phase. While GO:0006270 (DNA replication initiation) is more specific, this broader term is acceptable for capturing the overall replication process involvement. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md ORC binds sequence-defined ARS elements and, together with **Cdc6** and **Cdt1**, loads MCM2–7 to form the pre-RC |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation inferred from InterPro AAA+ ATPase domain (IPR003959). ORC1 catalyzes ATP hydrolysis for nucleotide-dependent conformational changes. Reason: Core molecular function. ORC1 is an AAA+ ATPase with documented ATP hydrolysis activity. This is essential for ORC complex assembly, DNA binding, and MCM loading. Experimental evidence (IMP PMID:9038340) supports this. Falcon deep research notes Orc1 is the only ORC subunit experimentally demonstrated to possess ATPase activity, reinforcing this as a core enzymatic function. Supporting Evidence: PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 is the only ORC subunit experimentally demonstrated to have ATPase activity |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation from UniProtKB keyword reflects metal coordination in ORC1s ATP binding sites. Reason: Technically correct - ORC1 binds Mg(2+) ions at ATP binding sites (documented in UniProt). However, this is a mechanistic detail subordinate to ATP binding and hydrolysis. The more specific ATP-related terms are more informative. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | KEEP AS NON CORE | Summary: IPI annotation from proteome survey identifies ORC1 interactions with ORC complex members and other proteins. Reason: Generic protein binding annotation. While experimentally supported (IPI), this term lacks specificity. ORC1 has well-characterized interactions with ORC2, ORC3, ORC4, ORC5, ORC6, MCM10, TAH11, and SIR1, but the generic binding term obscures these specific interactions. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | KEEP AS NON CORE | Summary: IPI annotation from global protein complex map confirms ORC1 protein-protein interactions. Reason: Duplicate IPI annotation for generic protein binding. While experimentally valid, this is non-specific. ORC1s binding partners are well-characterized at molecular level but the broad protein binding term is uninformative. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae |
| GO:0005515 protein binding | IPI PMID:17825065 Yeast two-hybrid analysis of the origin recognition complex ... | KEEP AS NON CORE | Summary: IPI annotation from yeast two-hybrid screen documents protein-protein interactions. Reason: Generic protein binding annotation supported by yeast two-hybrid data. While valid, the term lacks specificity regarding which proteins interact with ORC1. Supporting Evidence: PMID:17825065 Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins |
| GO:0005515 protein binding | IPI PMID:18647841 The architecture of the DNA replication origin recognition c... | KEEP AS NON CORE | Summary: IPI annotation from structural studies of ORC complex architecture documents protein interactions. Reason: Generic protein binding term. While the cryo-EM structure reveals ORC1 interactions with other ORC subunits, the broad binding term lacks mechanistic specificity. Supporting Evidence: PMID:18647841 The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | KEEP AS NON CORE | Summary: IPI annotation from chromatin-associated interactome defines ORC1 protein associations. Reason: Generic protein binding. Experimentally supported but non-specific for ORC1s characterized interactions. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome |
| GO:0005515 protein binding | IPI PMID:22405012 Cdc6-induced conformational changes in ORC bound to origin D... | KEEP AS NON CORE | Summary: IPI annotation from cryo-EM structural analysis documents ORC1 protein-protein contacts. Reason: Generic protein binding. Cryo-EM structure reveals detailed ORC subunit interactions, but broad binding term fails to capture this specificity. Supporting Evidence: PMID:22405012 Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | KEEP AS NON CORE | Summary: IPI annotation from inter-species protein interaction network identifies ORC1 protein interactions. Reason: Generic protein binding annotation. While documenting evolutionary conservation of protein interactions, the broad term lacks specificity. Supporting Evidence: PMID:27107014 An inter-species protein-protein interaction network across vast evolutionary distance |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | KEEP AS NON CORE | Summary: IPI annotation from social and structural architecture study confirms ORC1 protein associations. Reason: Generic protein binding. Recent interactome study confirms ORC1 interactions but the broad term is non-informative. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome |
| GO:0005515 protein binding | IPI PMID:8622770 Role of interactions between the origin recognition complex ... | KEEP AS NON CORE | Summary: IPI annotation documents ORC1-SIR1 interaction critical for transcriptional silencing function. Reason: Generic protein binding annotation. While the ORC1-SIR1 interaction is critical for silent locus silencing (and documented in UniProt interactions), the broad binding term obscures this mechanistically important interaction. Supporting Evidence: PMID:8622770 Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing |
| GO:0005634 nucleus | EXP PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | KEEP AS NON CORE | Summary: EXP annotation documents nuclear localization of ORC1 from in vitro reconstitution studies. Reason: Experimentally validated localization. However, nucleus is a broad cellular compartment term. The more specific nucleoplasm annotations (GO:0005654 TAS) and nuclear pre-replicative complex (GO:0005656 IDA) better describe ORC1s functional location. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0006270 DNA replication initiation | NAS PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: NAS (Not Annotated Source) evidence from reconstitution studies documents ORC1s essential role in initiation. Reason: Duplicate annotation for core function with different evidence type (NAS). The in vitro reconstitution studies provide mechanistic support for ORC1s role in pre-replicative complex assembly and DNA replication initiation. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0034728 nucleosome organization | IMP PMID:37020028 Establishment and function of chromatin organization at repl... | ACCEPT | Summary: IMP annotation from recent study characterizes ORC1s role in chromatin organization at replication origins. Reason: ORC1s BAH domain mediates nucleosome binding and influences nucleosome positioning at replication origins. This facilitates origin activation and is a documented secondary function. Experimental (IMP) evidence provides functional validation. Supporting Evidence: PMID:37020028 Establishment and function of chromatin organization at replication origins file:yeast/ORC1/ORC1-deep-research-falcon.md Structural work shows Orc1 BAH binds the nucleosome core directly |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749345 | KEEP AS NON CORE | Summary: TAS annotation from Reactome identifies nucleoplasm as the functional compartment for MCM loading. Reason: Correct subcellular localization but redundant with nucleus and nuclear pre-replicative complex annotations. Nucleoplasm is the appropriate compartment for ORC1 function but this is implicit in its replication initiation role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749381 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway identifies nucleoplasm localization during CDT1 release. Reason: Correct but redundant subcellular localization. Multiple pathway annotations for nucleoplasm are unnecessary. |
| GO:0005654 nucleoplasm | TAS Reactome:R-SCE-9749401 | KEEP AS NON CORE | Summary: TAS annotation from Reactome identifies nucleoplasm during MCM double hexamer formation. Reason: Correct but redundant subcellular localization. This duplicates the nucleoplasm annotation from other Reactome pathways. |
| GO:0031491 nucleosome binding | IDA PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex. | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s BAH domain interaction with nucleosomes. Reason: Experimental evidence (IDA) from structural and functional studies. ORC1s BAH domain specifically binds nucleosomes, facilitating nucleosome-mediated origin regulation. This is a characterized and important secondary function. Supporting Evidence: PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex file:yeast/ORC1/ORC1-deep-research-falcon.md A structural study determined the Orc1 BAH–nucleosome complex at **3.3 Å** and reported that Orc1 BAH forms extensive contacts with core histones, **burying ~1590 Ų** of surface |
| GO:0043007 maintenance of rDNA | IDA PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex. | ACCEPT | Summary: IDA annotation documents ORC1s role in ribosomal DNA maintenance and nucleosome organization at rDNA loci. Reason: Experimental evidence (IDA) supports ORC1s function in rDNA maintenance through nucleosome-based regulation. rDNA regions contain active replication origins and require specialized chromatin organization. This is a characterized secondary function. Falcon deep research adds that Orc1 BAH-nucleosome binding protects rDNA border integrity during meiosis, with reduced BAH affinity increasing double-strand breaks. Supporting Evidence: PMID:31263106 Structure and function of the Orc1 BAH-nucleosome complex file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 BAH–nucleosome interactions contribute to genome stability at rDNA borders during meiosis; reduced Orc1-BAH affinity is associated with increased double-strand breaks |
| GO:0003682 chromatin binding | IDA PMID:11168584 Interactions between Mcm10p and other replication factors ar... | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s chromatin binding through interactions with MCM10 and other chromatin factors. Reason: Experimental evidence (IDA) for chromatin binding. While not as specific as DNA replication origin binding or nucleosome binding, this annotation correctly captures ORC1s broader chromatin association function. Supporting Evidence: PMID:11168584 Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae |
| GO:0003688 DNA replication origin binding | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: IDA annotation provides direct experimental evidence for ORC1s origin binding function. Reason: Core molecular function. Direct assay evidence (IDA) from in vitro reconstitution unequivocally demonstrates ORC1s specific binding to origin DNA at ARS consensus sequences. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0005524 ATP binding | IDA PMID:17825064 Interaction between ORC and Cdt1p of Saccharomyces cerevisia... | ACCEPT | Summary: IDA annotation directly assays ATP binding in ORC1 and Cdt1 interaction studies. Reason: Core molecular function. Direct experimental evidence (IDA) confirms ATP binding. This is mechanistically essential for ORC1s regulatory ATPase activity. Supporting Evidence: PMID:17825064 Interaction between ORC and Cdt1p of Saccharomyces cerevisiae |
| GO:0005524 ATP binding | IMP PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPas... | ACCEPT | Summary: IMP annotation documents ATP binding as essential for ORC complex ATPase activity regulation. Reason: Core function. Mutational/functional evidence (IMP) shows ATP binding is required for coordinate regulation of origin binding and ATPase activity. Duplicates the IDA annotation but different evidence code validates importance. Supporting Evidence: PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex |
| GO:0005634 nucleus | IDA PMID:11168584 Interactions between Mcm10p and other replication factors ar... | KEEP AS NON CORE | Summary: IDA annotation directly demonstrates nuclear localization of ORC1. Reason: Experimental validation of nuclear localization. However, this broad cellular component term is less informative than the nuclear pre-replicative complex and nucleoplasm annotations that specify ORC1s functional compartments. Supporting Evidence: PMID:11168584 Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae |
| GO:0005656 nuclear pre-replicative complex | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: IDA annotation directly identifies ORC1 as a structural component of the pre-replicative complex. Reason: Core cellular component. ORC1 is a required component of the nuclear pre-replicative complex (pre-RC) that forms at G1. Experimental evidence (IDA) from in vitro reconstitution and cellular studies confirms this. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro |
| GO:0005656 nuclear pre-replicative complex | IDA PMID:9335335 Components and dynamics of DNA replication complexes in S. c... | ACCEPT | Summary: IDA annotation from cell cycle studies documents ORC1 as core component of pre-RC during S phase. Reason: Duplicate annotation for core component. Experimental evidence (IDA) from MCM protein redistribution studies confirms ORC1s role in pre-RC assembly and dynamics. Supporting Evidence: PMID:9335335 Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase |
| GO:0005664 nuclear origin of replication recognition complex | IDA PMID:9372948 Architecture of the yeast origin recognition complex bound t... | ACCEPT | Summary: IDA annotation directly identifies ORC1 as integral component of the ORC complex through structural analysis. Reason: Core cellular component. ORC1 is essential to ORC complex assembly. Experimental evidence (IDA) from origin-bound ORC architecture studies provides direct confirmation. Supporting Evidence: PMID:9372948 Architecture of the yeast origin recognition complex bound to origins of DNA replication |
| GO:0005664 nuclear origin of replication recognition complex | IMP PMID:9372948 Architecture of the yeast origin recognition complex bound t... | ACCEPT | Summary: IMP annotation documents ORC1s functional role in ORC complex assembly through mutational analysis. Reason: Core component. Duplicate annotation with different evidence type (IMP). Functional mutations demonstrate ORC1s essential role in complex formation and origin recognition. Supporting Evidence: PMID:9372948 Architecture of the yeast origin recognition complex bound to origins of DNA replication |
| GO:0006267 pre-replicative complex assembly involved in nuclear cell cycle DNA replication | IDA PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative co... | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s active role in pre-replicative complex assembly through in vitro reconstitution. Reason: Core biological process. ORC1 is the rate-limiting or nucleation factor for pre-RC assembly. Experimental evidence (IDA, IMP) from multiple studies unambiguously supports this essential function. Supporting Evidence: PMID:16824194 Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro file:yeast/ORC1/ORC1-deep-research-falcon.md ORC bends DNA at origin elements in a manner that helps align and insert DNA into the MCM ring during formation of helicase-loading intermediates |
| GO:0006267 pre-replicative complex assembly involved in nuclear cell cycle DNA replication | IMP PMID:9335335 Components and dynamics of DNA replication complexes in S. c... | ACCEPT | Summary: IMP annotation from cell cycle studies documents ORC1s essential role in pre-RC assembly. Reason: Duplicate annotation for core process. Experimental evidence (IMP) from MCM redistribution and functional studies confirms ORC1s requirement for pre-RC assembly. Supporting Evidence: PMID:9335335 Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase |
| GO:0006270 DNA replication initiation | IMP PMID:16716188 Cell cycle execution point analysis of ORC function and char... | ACCEPT | Summary: IMP annotation documents ORC1s essential role in DNA replication initiation through checkpoint and cell cycle execution point analysis. Reason: Core biological process. Conditional inactivation of ORC (including ORC1) results in failure of replication initiation, confirming essential role. Supporting Evidence: PMID:16716188 Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae |
| GO:0016887 ATP hydrolysis activity | IMP PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPas... | ACCEPT | Summary: IMP annotation demonstrates ATP hydrolysis activity is functionally essential for ORC1s regulatory mechanism. Reason: Core molecular function. Experimental evidence (IMP) shows ORC1s ATP hydrolysis is required for complex assembly and origin regulation. Mutations affecting ATPase activity impair ORC function. Supporting Evidence: PMID:9038340 Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex |
| GO:0030466 silent mating-type cassette heterochromatin formation | IDA PMID:12897051 Differential DNA affinity specifies roles for the origin rec... | ACCEPT | Summary: IDA annotation directly demonstrates ORC1s role in transcriptional silencing at HMR/HML loci. Reason: Core function. ORC1s interaction with SIR1 and other SIR proteins is essential for establishing heterochromatin at silent mating-type loci. Experimental evidence (IDA) from differential DNA affinity studies confirms this role. Falcon deep research clarifies the mechanism: the Orc1 BAH domain binds silencer elements and recruits Sir1, which nucleates the Sir2/Sir3/Sir4 silencing machinery, and shows this silencing-locus binding is genetically separable from origin binding (BAH deletion abolishes silencing-site binding but not origin binding). Supporting Evidence: PMID:12897051 Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 BAH binds at DNA silencer elements and recruits **Sir1**, which then helps recruit the Sir2/Sir3/Sir4 silencing machinery file:yeast/ORC1/ORC1-deep-research-falcon.md Orc1 lacking the BAH domain is **lost from silencing-associated sites but remains bound to replication origins** |
| GO:0030466 silent mating-type cassette heterochromatin formation | IDA PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 ... | ACCEPT | Summary: IDA annotation directly confirms ORC1-SIR3 interaction in heterochromatin establishment. Reason: Duplicate annotation for core silencing function. Experimental evidence (IDA) from Sir3 BAH domain structure studies demonstrates ORC1s functional role in recruiting silencing machinery. Supporting Evidence: PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain |
| GO:0030466 silent mating-type cassette heterochromatin formation | IGI PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 ... | ACCEPT | Summary: IGI annotation documents genetic interaction between ORC1 and SIR3 in heterochromatin formation. Reason: Genetic interaction evidence (IGI) supports ORC1s role in silencing. ORC1-SIR3 genetic interaction (with SGD:S000001809 = SIR3) demonstrates functional interdependence in establishing silent loci. Supporting Evidence: PMID:16581798 Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain |
| GO:0031261 DNA replication preinitiation complex | IDA PMID:9554851 Formation of a preinitiation complex by S-phase cyclin CDK-d... | ACCEPT | Summary: IDA annotation directly identifies ORC1 as component of preinitiation complex formed during S phase. Reason: Related to core function. ORC1 is part of the pre-initiation complex (loaded Cdc45). Experimental evidence (IDA) confirms ORC1s presence in this complex. Closely related to pre-replicative complex annotations. Supporting Evidence: PMID:9554851 Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin |
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Download this section (compressed HTML)Q: What is the functional role of ORC1s N-terminal domain versus C-terminal ATPase domain in origin recognition versus silencing?
Q: How does ORC1s BAH domain nucleosome binding affect MCM loading efficiency and origin firing timing?
Q: Why does ORC1 have dual roles in both replication initiation and transcriptional silencing - are these mechanistically linked?
Experiment: Structural analysis of ORC1 bound to both origin DNA and nucleosomes simultaneously to understand coordination
Type: Structural biology (Cryo-EM, X-ray crystallography)
Experiment: Single-molecule studies of MCM loading kinetics with wild-type versus nucleosome-binding deficient ORC1
Type: Biophysics
Experiment: Quantitative analysis of SIR protein recruitment and heterochromatin spreading at silent loci versus origin binding sites
Type: Quantitative cell biology
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