- EMDB-19566: Human OCCM DNA licensing intermediate -
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基本情報
登録情報
データベース: EMDB / ID: EMD-19566
タイトル
Human OCCM DNA licensing intermediate
マップデータ
試料
複合体: hOCCM
タンパク質・ペプチド: x 12種
DNA: x 2種
キーワード
DNA Replication / MCM2-7 / DNA licensing / human / origin / ORC / pre-RC / Cdc6 / Cdt1 / REPLICATION
機能・相同性
機能・相同性情報
DNA replication preinitiation complex assembly / response to sorbitol / positive regulation of chromosome segregation / cellular response to vasopressin / polar body extrusion after meiotic divisions / CDC6 association with the ORC:origin complex / origin recognition complex / positive regulation of DNA-templated DNA replication / regulation of nuclear cell cycle DNA replication / E2F-enabled inhibition of pre-replication complex formation ...DNA replication preinitiation complex assembly / response to sorbitol / positive regulation of chromosome segregation / cellular response to vasopressin / polar body extrusion after meiotic divisions / CDC6 association with the ORC:origin complex / origin recognition complex / positive regulation of DNA-templated DNA replication / regulation of nuclear cell cycle DNA replication / E2F-enabled inhibition of pre-replication complex formation / Switching of origins to a post-replicative state / Unwinding of DNA / negative regulation of DNA-templated DNA replication / nuclear origin of replication recognition complex / traversing start control point of mitotic cell cycle / Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence / alpha DNA polymerase:primase complex / mitotic DNA replication / DNA replication checkpoint signaling / attachment of mitotic spindle microtubules to kinetochore / CMG complex / inner kinetochore / regulation of phosphorylation / nuclear pre-replicative complex / DNA replication preinitiation complex / MCM complex / mitotic DNA replication checkpoint signaling / double-strand break repair via break-induced replication / mitotic DNA replication initiation / Transcription of E2F targets under negative control by DREAM complex / positive regulation of chromatin binding / neural precursor cell proliferation / regulation of mitotic metaphase/anaphase transition / regulation of cyclin-dependent protein serine/threonine kinase activity / regulation of DNA-templated DNA replication initiation / DNA strand elongation involved in DNA replication / cochlea development / negative regulation of DNA replication / G1/S-Specific Transcription / positive regulation of cytokinesis / regulation of DNA replication / negative regulation of cell cycle / DNA replication origin binding / cellular response to angiotensin / protein polymerization / Activation of the pre-replicative complex / DNA replication initiation / spindle midzone / glial cell proliferation / heterochromatin / Activation of ATR in response to replication stress / intercellular bridge / DNA polymerase binding / protein serine/threonine kinase binding / cellular response to epidermal growth factor stimulus / Assembly of the ORC complex at the origin of replication / cellular response to interleukin-4 / positive regulation of DNA replication / Assembly of the pre-replicative complex / kinetochore / CDK-mediated phosphorylation and removal of Cdc6 / Orc1 removal from chromatin / positive regulation of fibroblast proliferation / spindle pole / mitotic spindle / cellular response to xenobiotic stimulus / nucleosome assembly / mitotic cell cycle / single-stranded DNA binding / DNA helicase / histone binding / forked DNA-dependent helicase activity / single-stranded 3'-5' DNA helicase activity / four-way junction helicase activity / double-stranded DNA helicase activity / chromosome, telomeric region / cell population proliferation / DNA replication / nuclear body / cilium / negative regulation of cell population proliferation / cell division / nucleotide binding / intracellular membrane-bounded organelle / apoptotic process / centrosome / DNA damage response / chromatin binding / chromatin / nucleolus / perinuclear region of cytoplasm / enzyme binding / negative regulation of transcription by RNA polymerase II / ATP hydrolysis activity / DNA binding / zinc ion binding / nucleoplasm / ATP binding / metal ion binding / identical protein binding 類似検索 - 分子機能
CDT1 Geminin-binding domain-like / DNA replication factor Cdt1 / DNA replication factor CDT1 like / DNA replication factor CDT1 like / DNA replication factor Cdt1, C-terminal / DNA replication factor Cdt1, C-terminal WH domain superfamily / DNA replication factor Cdt1 C-terminal domain / Cell division protein Cdc6/18 / : / Cdc6/ORC-like, ATPase lid domain ...CDT1 Geminin-binding domain-like / DNA replication factor Cdt1 / DNA replication factor CDT1 like / DNA replication factor CDT1 like / DNA replication factor Cdt1, C-terminal / DNA replication factor Cdt1, C-terminal WH domain superfamily / DNA replication factor Cdt1 C-terminal domain / Cell division protein Cdc6/18 / : / Cdc6/ORC-like, ATPase lid domain / Origin recognition complex subunit 3, insertion domain / Origin recognition complex subunit 3 insertion domain / CDC6, C terminal / Cdc6, C-terminal / CDC6, C terminal winged helix domain / Origin recognition complex subunit 4 / Origin recognition complex, subunit 3 / Origin recognition complex, subunit 5 / Origin recognition complex subunit 4, C-terminal / Origin recognition complex subunit 3, winged helix C-terminal / Origin recognition complex subunit 3, N-terminal / : / : / Origin recognition complex (ORC) subunit 3 N-terminus / Origin recognition complex (ORC) subunit 4 C-terminus / Origin recognition complex (ORC) subunit 5 C-terminus / Origin recognition complex winged helix C-terminal / ORC5, lid domain / Orc1-like, AAA ATPase domain / Origin recognition complex subunit 2 RecA-like domain / AAA ATPase domain / Origin recognition complex, subunit 2 / DNA replication licensing factor MCM2-like, winged-helix domain / AAA lid domain / AAA lid domain / : / MCM3-like, winged helix domain / DNA replication licensing factor Mcm3 / Mini-chromosome maintenance complex protein 4 / DNA replication licensing factor Mcm6 / DNA replication licensing factor Mcm7 / Mcm6, C-terminal winged-helix domain / MCM6 C-terminal winged-helix domain / DNA replication licensing factor Mcm2 / Mini-chromosome maintenance protein 2 / Mini-chromosome maintenance, conserved site / MCM family signature. / Bromo adjacent homology domain / BAH domain / Bromo adjacent homology (BAH) domain / Bromo adjacent homology (BAH) domain superfamily / BAH domain profile. / MCM N-terminal domain / MCM N-terminal domain / MCM OB domain / MCM OB domain / Mini-chromosome maintenance protein / MCM, AAA-lid domain / MCM P-loop domain / MCM AAA-lid domain / MCM family domain profile. / minichromosome maintenance proteins / MCM domain / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / Nucleic acid-binding, OB-fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Origin recognition complex subunit 5 / Origin recognition complex subunit 4 / DNA replication licensing factor MCM3 / DNA replication licensing factor MCM4 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM2 / Origin recognition complex subunit 1 / Origin recognition complex subunit 2 / DNA replication licensing factor MCM6 / Cell division control protein 6 homolog ...Origin recognition complex subunit 5 / Origin recognition complex subunit 4 / DNA replication licensing factor MCM3 / DNA replication licensing factor MCM4 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM2 / Origin recognition complex subunit 1 / Origin recognition complex subunit 2 / DNA replication licensing factor MCM6 / Cell division control protein 6 homolog / DNA replication factor Cdt1 / Origin recognition complex subunit 3 類似検索 - 構成要素
ジャーナル: Nat Commun / 年: 2025 タイトル: Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates. 著者: Jennifer N Wells / Lucy V Edwardes / Vera Leber / Shenaz Allyjaun / Matthew Peach / Joshua Tomkins / Antonia Kefala-Stavridi / Sarah V Faull / Ricardo Aramayo / Carolina M Pestana / Lepakshi ...著者: Jennifer N Wells / Lucy V Edwardes / Vera Leber / Shenaz Allyjaun / Matthew Peach / Joshua Tomkins / Antonia Kefala-Stavridi / Sarah V Faull / Ricardo Aramayo / Carolina M Pestana / Lepakshi Ranjha / Christian Speck / 要旨: Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase ...Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins. We showed that the in vitro reaction is specific and results in the assembly of high-salt resistant hMCM2-7 double-hexamers. With ATPγS, an hORC1-5-hCDC6-hCDT1-hMCM2-7 (hOCCM) assembles independent of hORC6, but hORC6 enhances double-hexamer formation. We determined the hOCCM structure, which showed that hORC-hCDC6 recruits hMCM2-7 via five hMCM winged-helix domains. The structure highlights how hORC1 activates the hCDC6 ATPase and uncovered an unexpected role for hCDC6 ATPase in complex disassembly. We identified that hCDC6 binding to hORC1-5 stabilises hORC2-DNA interactions and supports hMCM3-dependent recruitment of hMCM2-7. Finally, the structure allowed us to locate cancer-associated mutations at the hCDC6-hMCM3 interface, which showed specific helicase loading defects.