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-Structure paper
Title | Structure of a human replisome shows the organisation and interactions of a DNA replication machine. |
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Journal, issue, pages | EMBO J, Vol. 40, Issue 23, Page e108819, Year 2021 |
Publish date | Dec 1, 2021 |
![]() | Morgan L Jones / Yasemin Baris / Martin R G Taylor / Joseph T P Yeeles / ![]() |
PubMed Abstract | 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 ...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. |
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Methods | EM (single particle) |
Resolution | 3.2 - 4.3 Å |
Structure data | EMDB-13375, PDB-7pfo: ![]() EMDB-13376: ![]() EMDB-13377: ![]() EMDB-13384: ![]() EMDB-13457: |
Chemicals | ![]() ChemComp-ZN: ![]() ChemComp-MG: ![]() ChemComp-ANP: ![]() ChemComp-SO4: |
Source |
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![]() | REPLICATION / DNA replication / helicase / CMG / TIMELESS / TIPIN / CLASPIN / AND-1 / EPSILON / POLYMERASE / REPLISOME |