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Structure paper

TitleArchaeal and eukaryotic MCM rings sequentially melt DNA for replication initiation.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateMar 31, 2026
AuthorsSanaz Rasouli / Alexander Myasnikov / Eric J Enemark /
PubMed AbstractDNA 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 linksNat Commun / PubMed:41916983 / PubMed Central
MethodsEM (single particle)
Resolution2.45 - 4.04 Å
Structure data

EMDB-49806, PDB-9nuh:
SsoPfMCM:DNA class 1a from merged particles
Method: EM (single particle) / Resolution: 2.92 Å

EMDB-49807, PDB-9nui:
SsoPfMCM:DNA class 1b from merged particles
Method: EM (single particle) / Resolution: 3.24 Å

EMDB-49808, PDB-9nuj:
SsoPfMCM:DNA class 1c from merged particles
Method: EM (single particle) / Resolution: 3.44 Å

EMDB-49809, PDB-9nuk:
SsoPfMCM:DNA class 2a from merged particles
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-49810, PDB-9nul:
SsoPfMCM:DNA class 2b from merged particles
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-49811, PDB-9num:
SsoPfMCM:DNA class 3 from merged particles
Method: EM (single particle) / Resolution: 3.67 Å

EMDB-49812, PDB-9nun:
SsoPfMCM:DNA class 1a from DNA 1
Method: EM (single particle) / Resolution: 3.36 Å

EMDB-49813, PDB-9nuo:
SsoPfMCM:DNA class 1b from DNA 1
Method: EM (single particle) / Resolution: 3.58 Å

EMDB-49814, PDB-9nup:
SsoPfMCM:DNA class 1c from DNA 1
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-49815, PDB-9nuq:
SsoPfMCM:DNA class 2a from DNA 1
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-49816, PDB-9nur:
SsoPfMCM:DNA class 2b from DNA 1
Method: EM (single particle) / Resolution: 2.99 Å

EMDB-49817, PDB-9nus:
SsoPfMCM:DNA class 3 from DNA 1
Method: EM (single particle) / Resolution: 4.04 Å

EMDB-49818, PDB-9nut:
SsoPfMCM:DNA class 1a from DNA 2
Method: EM (single particle) / Resolution: 2.93 Å

EMDB-49819, PDB-9nuu:
SsoPfMCM:DNA class 1b from DNA 2
Method: EM (single particle) / Resolution: 3.38 Å

EMDB-49820, PDB-9nuv:
SsoPfMCM:DNA class 1c from DNA 2
Method: EM (single particle) / Resolution: 3.51 Å

EMDB-49821, PDB-9nuw:
SsoPfMCM:DNA class 2a from DNA 2
Method: EM (single particle) / Resolution: 2.65 Å

EMDB-49822, PDB-9nux:
SsoPfMCM:DNA class 2b from DNA 2
Method: EM (single particle) / Resolution: 2.45 Å

EMDB-49823, PDB-9nuy:
SsoPfMCM:DNA class 3 from DNA 2
Method: EM (single particle) / Resolution: 3.52 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

Source
  • saccharolobus solfataricus p2 (archaea)
  • pyrococcus furiosus dsm 3638 (archaea)
  • synthetic construct (others)
KeywordsREPLICATION / HYDROLASE/DNA / DNA replication / helicase / MCM / HYDROLASE- DNA complex / HYDROLASE-DNA complex

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