Structure of a human replisome shows the organisation and interactions of a DNA replication machine.
Taylor, Martin RG
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Jones, M. L., Baris, Y., Taylor, M. R., & Yeeles, J. T. (2021). Structure of a human replisome shows the organisation and interactions of a DNA replication machine.. EMBO J https://doi.org/10.15252/embj.2021108819
The 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 ε, 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 Å cryo-EM structure of a human replisome comprising CMG, Pol ε, 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 ε engage CMG, reveals how CLASPIN binds to multiple replisome components and identifies the position of the Pol ε 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.
CMG helicase, DNA replication, cryo-EM, fork protection complex, replisome, Adaptor Proteins, Signal Transducing, Cell Cycle Proteins, Cytoskeletal Proteins, DNA Polymerase II, DNA Replication, DNA-Binding Proteins, Humans, Intracellular Signaling Peptides and Proteins, Models, Molecular, Poly-ADP-Ribose Binding Proteins, Protein Conformation
Medical Research Council (MC_UP_1201/12)
Wellcome Trust (110014/Z/15/Z)
External DOI: https://doi.org/10.15252/embj.2021108819
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329845
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