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dc.contributor.authorJones, Morgan L
dc.contributor.authorBaris, Yasemin
dc.contributor.authorTaylor, Martin RG
dc.contributor.authorYeeles, Joseph TP
dc.date.accessioned2021-10-25T11:11:02Z
dc.date.available2021-10-25T11:11:02Z
dc.date.issued2021-12-01
dc.date.submitted2021-05-27
dc.identifier.issn0261-4189
dc.identifier.otherembj2021108819
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329845
dc.description.abstractThe 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.
dc.languageen
dc.publisherEMBO
dc.subjectEMBO13
dc.subjectEMBO40
dc.subjectArticle
dc.subjectArticles
dc.subjectCMG helicase
dc.subjectcryo‐EM
dc.subjectDNA replication
dc.subjectfork protection complex
dc.subjectreplisome
dc.titleStructure of a human replisome shows the organisation and interactions of a DNA replication machine.
dc.typeArticle
dc.date.updated2021-10-25T11:11:02Z
prism.publicationNameEMBO J
dc.identifier.doi10.17863/CAM.77290
dcterms.dateAccepted2021-09-30
rioxxterms.versionofrecord10.15252/embj.2021108819
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidJones, Morgan L [0000-0003-1948-4925]
dc.contributor.orcidBaris, Yasemin [0000-0003-2791-5588]
dc.contributor.orcidYeeles, Joseph TP [0000-0002-2255-2119]
dc.identifier.eissn1460-2075
pubs.funder-project-idMedical Research Council (MC_UP_1201/12)
pubs.funder-project-idWellcome Trust (110014/Z/15/Z)
cam.issuedOnline2021-10-25


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