Structural highlights
Function
MCM2_HUMAN Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division.[1]
Publication Abstract from PubMed
During eukaryotic DNA replication, Pol alpha-primase generates primers at replication origins to start leading-strand synthesis and every few hundred nucleotides during discontinuous lagging-strand replication. How Pol alpha-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 alpha-primase, we reveal a conserved mechanism for the coordination of priming by the replisome. Pol alpha-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 alpha-primase to overcome competition from RPA to initiate primer synthesis.
How Pol alpha-primase is targeted to replisomes to prime eukaryotic DNA replication.,Jones ML, Aria V, Baris Y, Yeeles JTP Mol Cell. 2023 Jul 27:S1097-2765(23)00511-7. doi: 10.1016/j.molcel.2023.06.035. PMID:37506699[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Todorov IT, Pepperkok R, Philipova RN, Kearsey SE, Ansorge W, Werner D. A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division. J Cell Sci. 1994 Jan;107 ( Pt 1):253-65. PMID:8175912
- ↑ Jones ML, Aria V, Baris Y, Yeeles JTP. How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication. Mol Cell. 2023 Jul 27:S1097-2765(23)00511-7. PMID:37506699 doi:10.1016/j.molcel.2023.06.035
