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	How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication.
Journal, issue, pages	Mol Cell, Vol. 83, Issue 16, Page 2911-2924.e16, Year 2023
Publish date	Aug 17, 2023
Authors	Morgan L Jones / Valentina Aria / Yasemin Baris / Joseph T P Yeeles /
PubMed Abstract	During eukaryotic DNA replication, Pol α-primase generates primers at replication origins to start leading-strand synthesis and every few hundred nucleotides during discontinuous lagging-strand ...During eukaryotic DNA replication, Pol α-primase generates primers at replication origins to start leading-strand synthesis and every few hundred nucleotides during discontinuous lagging-strand replication. How Pol α-primase is targeted to replication forks to prime DNA synthesis is not fully understood. Here, by determining cryoelectron microscopy (cryo-EM) structures of budding yeast and human replisomes containing Pol α-primase, we reveal a conserved mechanism for the coordination of priming by the replisome. Pol α-primase binds directly to the leading edge of the CMG (CDC45-MCM-GINS) replicative helicase via a complex interaction network. The non-catalytic PRIM2/Pri2 subunit forms two interfaces with CMG that are critical for in vitro DNA replication and yeast cell growth. These interactions position the primase catalytic subunit PRIM1/Pri1 directly above the exit channel for lagging-strand template single-stranded DNA (ssDNA), revealing why priming occurs efficiently only on the lagging-strand template and elucidating a mechanism for Pol α-primase to overcome competition from RPA to initiate primer synthesis.
External links	Mol Cell / PubMed:37506699 / PubMed Central
Methods	EM (single particle)
Resolution	2.98 - 8.75098 Å
Structure data	EMDB-15303: S. cerevisiae pol alpha bound to the core replisome engaged with a fork DNA substrate containing a 60 nucleotide lagging strand - unbinned. Method: EM (single particle) / Resolution: 3.34 Å EMDB-15304: Csm3/Tof1 local refinement - pol alpha bound replisome Method: EM (single particle) / Resolution: 3.93 Å EMDB-15305: C-tier local refinement, pol alpha - replisome complex. Locally filtered Method: EM (single particle) / Resolution: 3.23 Å EMDB-15306: Pol12, PolA1 and Pri2 N-terminal domain local refinement. Pol alpha - replisome complex. Method: EM (single particle) / Resolution: 5.04 Å 15309 8b9a 8b9b EMDB-15309: Pol alpha - replisome complex containing Ctf4. Engaged on a DNA fork containing a 60 nucleotide lagging strand. PDB-8b9a: S. cerevisiae replisome + Ctf4, bound by pol alpha primase. Complex engaged with a fork DNA substrate containing a 60 nucleotide lagging strand. PDB-8b9b: S. cerevisiae replisome + Ctf4, bound by pol alpha. Complex engaged with a fork DNA substrate containing a 60 nucleotide lagging strand. Method: EM (single particle) / Resolution: 4.64 Å EMDB-15310: Ctf4 - GINS - Cdc45 local refinement. Pol alpha - replisome complex. Method: EM (single particle) / Resolution: 3.33 Å EMDB-15340: MCM C-tier local refinement. Human replisome bound by pol alpha, engaged on fork DNA with 60 nt lagging strand. Method: EM (single particle) / Resolution: 3.7 Å 15341 8b9d EMDB-15341: Human replisome bound by pol alpha, engaged on fork DNA containing a 60 nt lagging strand. PDB-8b9d: Human replisome bound by Pol Alpha Method: EM (single particle) / Resolution: 3.4 Å EMDB-15342: AND-1, CDC45, GINS local refinement. Human replisome bound by pol alpha - engaged on a 60 nt lagging strand DNA fork substrate. Method: EM (single particle) / Resolution: 3.4 Å EMDB-15349: Human replisome bound by Pol Alpha, locally filtered. Strong PRIM1 density. Engaged on a fork DNA substrate containing a 60 nt lagging strand. Method: EM (single particle) / Resolution: 4.33 Å EMDB-15356: TIMELESS/TIPIN local refinement. Human replisome bound by Pol Alpha engaged on fork DNA with a 60 nt lagging strand. Method: EM (single particle) / Resolution: 4.05 Å EMDB-15902: S. cerevisiae replisome + Ctf4 + pol alpha. Unbinned, locally filtered. Method: EM (single particle) / Resolution: 3.5 Å EMDB-15904: Composite map - human replisome + Pol alpha Method: EM (single particle) / Resolution: 4.0 Å EMDB-15918: Human replisome + pol alpha. Not engaged on DNA. Method: EM (single particle) / Resolution: 3.6 Å EMDB-15922: Human replisome bound to pol alpha engaged on a DNA fork substrate containing a 15 nucleotide lagging strand. Method: EM (single particle) / Resolution: 3.3 Å EMDB-15923: Human replisome prepared in the presence of a fork DNA substrate containing a 60 nucleotide lagging strand. Off DNA. Method: EM (single particle) / Resolution: 3.6 Å 15924 8b9c EMDB-15924, PDB-8b9c: S. cerevisiae pol alpha - replisome complex Method: EM (single particle) / Resolution: 4.6 Å EMDB-16247: Local refinement, Pri1:Pri2-CTD. Pol alpha primase associated budding yeast replisome. Method: EM (single particle) / Resolution: 8.75098 Å EMDB-16248: Pol alpha primase associated budding yeast replisome. Consensus refinement containing clear density for the Pri2-CTD and Pol1 exo/cat domains. Method: EM (single particle) / Resolution: 4.61857 Å EMDB-16320: Pol-alpha primase associated replisome binned consensus refinement in the absence of Ctf4, 60 nucleotide 5'-flap DNA fork Method: EM (single particle) / Resolution: 4.64 Å EMDB-16322: Pol alpha-primase associated replisome unbinned consensus refinement in the absence of Ctf4, 60 nucleotide 5'-flap DNA fork Method: EM (single particle) / Resolution: 3.47 Å EMDB-16323: Un-binned consensus refinement of Pol alpha-primase associated with the replisome only via the Pri2:Mcm5ZnF interface, 60 nucleotide 5'-flap DNA fork Method: EM (single particle) / Resolution: 2.98 Å EMDB-16885: Pol12:Pol1CTD local refinement Method: EM (single particle) / Resolution: 4.8 Å
Chemicals	ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogueYM ChemComp-MG: Unknown entry ChemComp-ZN*: Unknown entry
Source	saccharomyces cerevisiae (brewer's yeast) homo sapiens (human)
Keywords	REPLICATION / helicase / polymerase / pol alpha / priming / replisome / human