Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Multiple mechanisms for licensing human replication origins.
Journal, issue, pages	Nature, Vol. 636, Issue 8042, Page 488-498, Year 2024
Publish date	Nov 27, 2024
Authors	Ran Yang / Olivia Hunker / Marleigh Wise / Franziska Bleichert /
PubMed Abstract	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 ...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.
External links	Nature / PubMed:39604729 / PubMed Central
Methods	EM (single particle)
Resolution	2.8 - 3.8 Å
Structure data	43707 8w0e EMDB-43707, PDB-8w0e: Cryo-EM structure of a human MCM2-7 single hexamer on dsDNA Method: EM (single particle) / Resolution: 3.4 Å 43708 8w0f EMDB-43708, PDB-8w0f: Cryo-EM structure of a human MCM2-7 double hexamer on dsDNA Method: EM (single particle) / Resolution: 2.8 Å 43709 8w0g EMDB-43709, PDB-8w0g: Cryo-EM structure of a human MCM2-7 dimer Method: EM (single particle) / Resolution: 3.8 Å 43710 8w0i EMDB-43710, PDB-8w0i: Cryo-EM structure of the human MCM2-7 heterohexamer Method: EM (single particle) / Resolution: 3.5 Å 45400 9caq EMDB-45400, PDB-9caq: Cryo-EM structure of a human MCM2-7 double hexamer formed from independently loaded MCM2-7 single hexamers Method: EM (single particle) / Resolution: 3.2 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM
Source	homo sapiens (human) saccharomyces cerevisiae (brewer's yeast)
Keywords	REPLICATION / complex / helicase / AAA+ ATPase / DNA BINDING PROTEIN