Rat AntiORC3 (origin recognition complex 3) Target Antigen ORC3 (origin recognition complex 3) Host Isotype Rat IgG2b Application IP; WB;
- Known as:
- Rat AntiORC3 (origin recognition aggregate 3) Target Antigen ORC3 (origin recognition aggregate 3) Host Isotype Rat IgG2b Application IP; Western Blot;
- Catalog number:
- IQ308
- Product Quantity:
- 50ul (1mg/ml)
- Category:
- -
- Supplier:
- Imunquest
- Gene target:
- Rat AntiORC3 (origin recognition complex 3) Target Antigen ORC3 Host Isotype IgG2b Application ;
Related genes to: Rat AntiORC3 (origin recognition complex 3) Target Antigen ORC3 (origin recognition complex 3) Host Isotype Rat IgG2b Application IP; WB;
- Gene:
- ORC3 NIH gene
- Name:
- origin recognition complex subunit 3
- Previous symbol:
- ORC3L
- Synonyms:
- IMAGE50150, LATHEO
- Chromosome:
- 6q15
- Locus Type:
- gene with protein product
- Date approved:
- 1999-11-16
- Date modifiied:
- 2016-10-05
Related products to: Rat AntiORC3 (origin recognition complex 3) Target Antigen ORC3 (origin recognition complex 3) Host Isotype Rat IgG2b Application IP; WB;
α - Calcitonin Gene Related Peptide, α - CGRP, rat'F 4_80 Antigen (mouse) Host Rat'F 4_80 Antigen (mouse) Host Rat(+)_Isopinocampheylborane tmeda complex(2_Furoyl)_PAR_2 (2_6)_Orn amide (mouse, rat) Salt Trifluoroacetate Binding _ Synonym (2_Furoyl)_LIGRLOamide SumFormula C36H63N11O8(2_Furoyl)_PAR_2 (2_6)_Orn amide (mouse, rat) Salt Trifluoroacetate Binding _ Synonym (2_Furoyl)_LIGRLOamide SumFormula C36H63N11O8(Ala11·22·28)_VIP (human, bovine, porcine, rat) Salt Trifluoroacetate Binding _ Synonym (Ala11·22·28)_Aviptadil SumFormula C139H231N43O39S(Ala11·22·28)_VIP (human, bovine, porcine, rat) Salt Trifluoroacetate Binding _ Synonym (Ala11·22·28)_Aviptadil SumFormula C139H231N43O39S(Ala13)-Apelin-13 (human, bovine, mouse, rat) 98% C63H107N23O16S CAS: 568565-11-7(Ala13)_Apelin_13 (human, bovine, mouse, rat) Salt Trifluoroacetate Binding _ Synonym SumFormula C63H107N23O16S(Ala13)_Apelin_13 (human, bovine, mouse, rat) Salt Trifluoroacetate Binding _ Synonym SumFormula C63H107N23O16S(Ala96)-Myelin Basic Protein (87-99) (human, bovine, rat) 98% C70H110N20O17 CAS:(Ala96)_Myelin Basic Protein (87_99) (human, bovine, rat) Salt _ Binding _ Synonym SumFormula C72H112N20O17(Ala96)_Myelin Basic Protein (87_99) (human, bovine, rat) Salt _ Binding _ Synonym SumFormula C72H112N20O17(Anti_Tg)Thyroglobulin Antigen Related articles to: Rat AntiORC3 (origin recognition complex 3) Target Antigen ORC3 (origin recognition complex 3) Host Isotype Rat IgG2b Application IP; WB;
- DNA replication initiation is a tightly regulated process that requires the coordinated assembly of replication machineries throughout the genome. During the first step of initiation, origin licensing, the MCM replicative helicase motor is loaded onto replication origins by the origin recognition complex (ORC) as a head-to-head double hexamer complex. Distinct mechanisms have been proposed to facilitate human MCM double hexamer loading, but the physiological relevance of each of them remains unclear. Here, we investigate the evolutionary conservation of these pathways using an AlphaFold-guided structural phylogenetics approach. Our analyses reveal that ORC6, a subunit of ORC previously thought to be essential for origin licensing in vivo, has been lost in multiple metazoan lineages. Despite this loss, many of these species retain an element in ORC3, the ORC3 tether, that can interact with MCM and facilitate an ORC6-independent MCM loading mechanism. AlphaFold2 Multimer predictions suggest that ORC3 tether interactions with MCM are broadly conserved across Metazoa. Our findings support the physiological relevance of ORC6-independent MCM loading, provide experimentally testable hypotheses on origin licensing mechanisms in diverse metazoan species, and highlight how AlphaFold can be leveraged to investigate protein evolution and function over large timescales. - Source: PubMed
Publication date: 2025/11/27
Hunker OliviaBleichert Franziska - Cetaceans, well-known for their exceptionally long lifespans and substantial body masses, demonstrate a lower risk of cancer mortality compared to other mammals, consistent with Peto's paradox. Yet, the underlying mechanisms of cancer resistance, possibly evolved due to large body size, remain largely unclear. Here, we conducted an evolutionary analysis of 50 cell cycle-related genes, which play crucial role in both cancer progression and organismal body mass modulation, to investigate the mechanisms underlying the trade-off between body size and cancer resistance in cetaceans. We found that 66.7% (4/6) rapidly evolving genes (i.e. CDK2, CDT1, ORC3, and DBF4) and 50% (2/4) positively selected genes (ORC2 and ORC3) identified in cetaceans are involved in regulating cell cycle checkpoints, which halt the cell cycle in response to damage to allow repair and prevent cancer induction. Additionally, we identified four-body mass-associated genes (CCNE1, ORC5, E2F3, and DBF4) known to regulate cell growth; mutations or dysregulation of these genes can drive uncontrolled proliferation and cancer development. Interestingly, convergent evolution was observed in the African elephant and the bowhead whale at the tumor suppressor gene MYT1, potentially revealing a convergent mechanism of cancer resistance in large-bodied species. Notably, in vitro assays revealed that a cetacean-specific mutation M155T in the rapidly evolving gene CCND1 more effectively suppressed tumor cell proliferation and migration. Overall, our study has provided new insights into how the evolution of cell cycle-related genes balances body mass and cancer resistance in cetaceans, offering molecular support for Peto's paradox. - Source: PubMed
Sun LinxiaLi YiZhang HuijieChen XinruiYang GuangXu Shixia - In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), chromosomal translocations are strongly associated with prognoses. RNA sequencing (RNA-seq) is a powerful technology that reveals a close correlation between types of translocation and patterns of gene expression in clinical samples of BCP-ALL. Cancer cell lines are powerful research tools, and thus, we built a larger series of BCP-ALL cell lines and performed RNA-seq analysis to confirm their utility as a model system. - Source: PubMed
Tamai MinoriKomatsu ChiakiKagami KeikoKasai ShinAkahane KoshiGoi KumikoSugita KanjiTomoyasu ChihiroImamura ToshihikoGoto HiroakiInukai Takeshi - The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled. A cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate shows a remodelled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and specifically recognises this closed ring. Interestingly, we found that normal helicase loading triggers Mcm4 ATP-hydrolysis, which in turn leads to reorganisation of the MCM2-7 complex and Cdt1 release. However, defective MCM2-7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and complex disassembly. As such we identify Mcm4 as the key ATPase in regulating pre-RC formation. Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysis-dependent remodelling of the helicase. - Source: PubMed
Publication date: 2025/01/02
Faull Sarah VBarbon MartaMossler AudreyYuan ZuanningBai LinReuter L MaximilianRiera AlbertoWinkler ChristianMagdalou IndianaPeach MatthewLi HuilinSpeck Christian - Loading of replicative helicases is obligatory for the assembly of DNA replication machineries. The eukaryotic MCM2-7 replicative helicase motor is deposited onto DNA by the origin recognition complex (ORC) and co-loader proteins as a head-to-head double hexamer to license replication origins. Although extensively studied in budding yeast, the mechanisms of origin licensing in multicellular eukaryotes remain poorly defined. Here we use biochemical reconstitution and electron microscopy to reconstruct the human MCM loading pathway. We find that unlike in yeast, the ORC6 subunit of the ORC is not essential for-but enhances-human MCM loading. Electron microscopy analyses identify several intermediates en route to MCM double hexamer formation in the presence and absence of ORC6, including a DNA-loaded, closed-ring MCM single hexamer intermediate that can mature into a head-to-head double hexamer through multiple mechanisms. ORC6 and ORC3 facilitate the recruitment of the ORC to the dimerization interface of the first hexamer into MCM-ORC (MO) complexes that are distinct from the yeast MO complex and may orient the ORC for second MCM hexamer loading. Additionally, MCM double hexamer formation can proceed through dimerization of independently loaded MCM single hexamers, promoted by a propensity of human MCM2-7 hexamers to self-dimerize. This flexibility in human MCM loading may provide resilience against cellular replication stress, and the reconstitution system will enable studies addressing outstanding questions regarding DNA replication initiation and replication-coupled events in the future. - Source: PubMed
Publication date: 2024/11/27
Yang RanHunker OliviaWise MarleighBleichert Franziska