Structure of a human replisome shows the organisation and interactions of a DNA replication machine.
dc.contributor.author | Jones, Morgan L | |
dc.contributor.author | Baris, Yasemin | |
dc.contributor.author | Taylor, Martin RG | |
dc.contributor.author | Yeeles, Joseph TP | |
dc.date.accessioned | 2021-10-25T11:11:02Z | |
dc.date.available | 2021-10-25T11:11:02Z | |
dc.date.issued | 2021-12-01 | |
dc.date.submitted | 2021-05-27 | |
dc.identifier.issn | 0261-4189 | |
dc.identifier.other | embj2021108819 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/329845 | |
dc.description.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 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.language | en | |
dc.publisher | EMBO | |
dc.subject | EMBO13 | |
dc.subject | EMBO40 | |
dc.subject | Article | |
dc.subject | Articles | |
dc.subject | CMG helicase | |
dc.subject | cryo‐EM | |
dc.subject | DNA replication | |
dc.subject | fork protection complex | |
dc.subject | replisome | |
dc.title | Structure of a human replisome shows the organisation and interactions of a DNA replication machine. | |
dc.type | Article | |
dc.date.updated | 2021-10-25T11:11:02Z | |
prism.publicationName | EMBO J | |
dc.identifier.doi | 10.17863/CAM.77290 | |
dcterms.dateAccepted | 2021-09-30 | |
rioxxterms.versionofrecord | 10.15252/embj.2021108819 | |
rioxxterms.version | AO | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.contributor.orcid | Jones, Morgan L [0000-0003-1948-4925] | |
dc.contributor.orcid | Baris, Yasemin [0000-0003-2791-5588] | |
dc.contributor.orcid | Yeeles, Joseph TP [0000-0002-2255-2119] | |
dc.identifier.eissn | 1460-2075 | |
pubs.funder-project-id | Medical Research Council (MC_UP_1201/12) | |
pubs.funder-project-id | Wellcome Trust (110014/Z/15/Z) | |
cam.issuedOnline | 2021-10-25 |
Files in this item
This item appears in the following Collection(s)
-
Jisc Publications Router
This collection holds Cambridge publications received from the Jisc Publications Router