8B9D

Human replisome bound by Pol Alpha

This is a non-PDB format compatible entry.

Summary for 8B9D

• Entry DOI: 10.2210/pdb8b9d/pdb
• EMDB information: 15340 15341 15342 15349 15351 15356
• Descriptor: DNA replication licensing factor MCM2, DNA replication complex GINS protein PSF2, DNA replication complex GINS protein PSF3, ... (24 entities in total)
• Functional Keywords: human, replication, priming, polymerase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 23
• Total formula weight: 1834176.54

Authors

Jones, M.L.,Yeeles, J.T.P. (deposition date: 2022-10-05, release date: 2023-08-09, Last modification date: 2023-08-30)

Primary citation

Jones, M.L.,Aria, V.,Baris, Y.,Yeeles, J.T.P.
How Pol alpha-primase is targeted to replisomes to prime eukaryotic DNA replication.
Mol.Cell, 83:2911-, 2023

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 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.

PubMed: 37506699
DOI: 10.1016/j.molcel.2023.06.035

Experimental method

ELECTRON MICROSCOPY (3.4 Å)