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-Structure paper
| Title | Archaeal and eukaryotic MCM rings sequentially melt DNA for replication initiation. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 17, Issue 1, Year 2026 |
| Publish date | Mar 31, 2026 |
Authors | Sanaz Rasouli / Alexander Myasnikov / Eric J Enemark / ![]() |
| PubMed Abstract | DNA replication initiation requires local melting of fully base-paired DNA for a helicase to gain a foothold and initiate processive DNA unwinding. In eukaryotes and archaea, the helicase engine is ...DNA replication initiation requires local melting of fully base-paired DNA for a helicase to gain a foothold and initiate processive DNA unwinding. In eukaryotes and archaea, the helicase engine is the hexameric ring minichromosome maintenance (MCM) complex. In eukaryotes, a defined biochemical sequence assembles two Cdc45-MCM-GINS (CMG) complexes that provide limited DNA unwinding as the species that immediately precedes extensive unwinding. A prior structure revealed how MCM subunits interact with this form of DNA, but the atomic progression from undistorted DNA to this melted DNA species is unknown. Here, we present a sequential DNA melting mechanism determined by snapshots of an archaeal MCM ring with DNA in varying degrees of melting. In this mechanism, successive ATP-binding at MCM ATPase sites drives sequential discrete DNA melting steps mediated a specific MCM aromatic residue. Analysis of eukaryotic structures shows loaded MCM rings principally adopt only two molecular arrangements at the ATPase: one that does not melt DNA and one tuned to melt DNA with equivalent aromatic residues, indicating a universal sequential mechanism melts DNA in archaea and eukaryotes for replication initiation. |
External links | Nat Commun / PubMed:41916983 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.45 - 4.04 Å |
| Structure data | EMDB-49806, PDB-9nuh: EMDB-49807, PDB-9nui: EMDB-49808, PDB-9nuj: EMDB-49809, PDB-9nuk: EMDB-49810, PDB-9nul: EMDB-49811, PDB-9num: EMDB-49812, PDB-9nun: EMDB-49813, PDB-9nuo: EMDB-49814, PDB-9nup: EMDB-49815, PDB-9nuq: EMDB-49816, PDB-9nur: EMDB-49817, PDB-9nus: EMDB-49818, PDB-9nut: EMDB-49819, PDB-9nuu: EMDB-49820, PDB-9nuv: EMDB-49821, PDB-9nuw: EMDB-49822, PDB-9nux: EMDB-49823, PDB-9nuy: |
| Chemicals | ![]() ChemComp-ADP: ![]() ChemComp-MG: ![]() ChemComp-ZN: ![]() ChemComp-HOH: ![]() ChemComp-AGS: |
| Source |
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Keywords | REPLICATION / HYDROLASE/DNA / DNA replication / helicase / MCM / HYDROLASE- DNA complex / HYDROLASE-DNA complex |
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saccharolobus solfataricus p2 (archaea)
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