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	A conserved mechanism for regulating replisome disassembly in eukaryotes.
Journal, issue, pages	Nature, Vol. 600, Issue 7890, Page 743-747, Year 2021
Publish date	Oct 26, 2021
Authors	Michael Jenkyn-Bedford / Morgan L Jones / Yasemin Baris / Karim P M Labib / Giuseppe Cannone / Joseph T P Yeeles / Tom D Deegan /
PubMed Abstract	Replisome disassembly is the final step of eukaryotic DNA replication and is triggered by ubiquitylation of the CDC45-MCM-GINS (CMG) replicative helicase. Despite being driven by evolutionarily ...Replisome disassembly is the final step of eukaryotic DNA replication and is triggered by ubiquitylation of the CDC45-MCM-GINS (CMG) replicative helicase. Despite being driven by evolutionarily diverse E3 ubiquitin ligases in different eukaryotes (SCF in budding yeast, CUL2 in metazoa), replisome disassembly is governed by a common regulatory principle, in which ubiquitylation of CMG is suppressed before replication termination, to prevent replication fork collapse. Recent evidence suggests that this suppression is mediated by replication fork DNA. However, it is unknown how SCF and CUL2 discriminate terminated from elongating replisomes, to selectively ubiquitylate CMG only after termination. Here we used cryo-electron microscopy to solve high-resolution structures of budding yeast and human replisome-E3 ligase assemblies. Our structures show that the leucine-rich repeat domains of Dia2 and LRR1 are structurally distinct, but bind to a common site on CMG, including the MCM3 and MCM5 zinc-finger domains. The LRR-MCM interaction is essential for replisome disassembly and, crucially, is occluded by the excluded DNA strand at replication forks, establishing the structural basis for the suppression of CMG ubiquitylation before termination. Our results elucidate a conserved mechanism for the regulation of replisome disassembly in eukaryotes, and reveal a previously unanticipated role for DNA in preserving replisome integrity.
External links	Nature / PubMed:34700328 / PubMed Central
Methods	EM (single particle)
Resolution	2.8 - 12.0 Å
Structure data	EMDB-13490: ELONGIN-BC/LRR1/CUL2 multibody refinement Method: EM (single particle) / Resolution: 8.0 Å EMDB-13491: AND-1/CDC45/GINS multibody refinement Method: EM (single particle) / Resolution: 3.3 Å EMDB-13492: Multibody refinement CUL2/RXB1 Method: EM (single particle) / Resolution: 12.0 Å 13494 7plo EMDB-13494, PDB-7plo: H. sapiens replisome-CUL2/LRR1 complex Method: EM (single particle) / Resolution: 2.8 Å EMDB-13495: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation I) - full complex (unsharpened map) Method: EM (single particle) / Resolution: 3.9 Å EMDB-13496: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation I) - full complex (sharpened map) Method: EM (single particle) / Resolution: 3.4 Å EMDB-13497: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation I) - MCM N-tier region Method: EM (single particle) / Resolution: 3.3 Å EMDB-13498: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation I) - MCM C-tier region Method: EM (single particle) / Resolution: 3.3 Å EMDB-13500: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation II) - full complex (unsharpened map) Method: EM (single particle) / Resolution: 4.4 Å EMDB-13512: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation II) - full complex (sharpened map) Method: EM (single particle) / Resolution: 3.7 Å EMDB-13513: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation II) - MCM N-tier region Method: EM (single particle) / Resolution: 3.4 Å EMDB-13514: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA (conformation II) - MCM C-tier region Method: EM (single particle) / Resolution: 3.6 Å EMDB-13515: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA - region encompassing Dia2-Skp1 Method: EM (single particle) / Resolution: 4.0 Å EMDB-13516: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA - region encompassing Cdc45-GINS-Ctf4-Dpb2N Method: EM (single particle) / Resolution: 3.2 Å EMDB-13517: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA - region encompassing Pol2-Dpb2-Mcm5 WH Method: EM (single particle) / Resolution: 3.5 Å EMDB-13518: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, bound to dsDNA, enriched for particles containing Csm3-Tof1 Method: EM (single particle) / Resolution: 3.6 Å EMDB-13519: Cryo-EM reconstruction of the full S. cerevisiae replisome-SCF(Dia2) complex in the absence of DNA (unsharpened map) Method: EM (single particle) / Resolution: 8.3 Å EMDB-13534: Cryo-EM map of the core human replisome on a DNA substrate lacking a 5'-flap Method: EM (single particle) / Resolution: 3.1 Å 13537 7pmk EMDB-13537, PDB-7pmk: S. cerevisiae replisome-SCF(Dia2) complex bound to double-stranded DNA (conformation I) Method: EM (single particle) / Resolution: 3.2 Å 13539 7pmn EMDB-13539, PDB-7pmn: S. cerevisiae replisome-SCF(Dia2) complex bound to double-stranded DNA (conformation II) Method: EM (single particle) / Resolution: 3.2 Å EMDB-13540: Cryo-EM reconstruction of the S. cerevisiae replisome-SCF(Dia2) complex, in the absence of DNA - region encompassing MCM N-tier-Cdc45-GINS-Ctf4-Dia2 Method: EM (single particle) / Resolution: 3.9 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogueYM ChemComp-SO4*: SULFATE ION / Sulfate
Source	homo sapiens (human) saccharomyces cerevisiae (brewer's yeast) DNA molecule (others) synthetic construct (others)
Keywords	REPLICATION / Genome stability / DNA replication / Ubiquitination / termination / replisome / cryo-EM / CMG / Cul2LRR1 / DNA / polymerase / helicase / SCF(Dia2)