7pfo
From Proteopedia
Core human replisome
Structural highlights
FunctionMCM6_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.[1] Publication Abstract from PubMedThe human replisome is an elaborate arrangement of molecular machines responsible for accurate chromosome replication. At its heart is the CDC45-MCM-GINS (CMG) helicase, which, in addition to unwinding the parental DNA duplex, arranges many proteins including the leading-strand polymerase Pol epsilon, together with TIMELESS-TIPIN, CLASPIN and AND-1 that have key and varied roles in maintaining smooth replisome progression. How these proteins are coordinated in the human replisome is poorly understood. We have determined a 3.2 A cryo-EM structure of a human replisome comprising CMG, Pol epsilon, TIMELESS-TIPIN, CLASPIN and AND-1 bound to replication fork DNA. The structure permits a detailed understanding of how AND-1, TIMELESS-TIPIN and Pol epsilon engage CMG, reveals how CLASPIN binds to multiple replisome components and identifies the position of the Pol epsilon catalytic domain. Furthermore, the intricate network of contacts contributed by MCM subunits and TIMELESS-TIPIN with replication fork DNA suggests a mechanism for strand separation. Structure of a human replisome shows the organisation and interactions of a DNA replication machine.,Jones ML, Baris Y, Taylor MRG, Yeeles JTP EMBO J. 2021 Dec 1;40(23):e108819. doi: 10.15252/embj.2021108819. Epub 2021 Oct , 25. PMID:34694004[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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