Repository logo
 

Helicase Subunit Cdc45 Targets the Checkpoint Kinase Rad53 to Both Replication Initiation and Elongation Complexes after Fork Stalling.

Simple item page
cam.issuedOnline2018-12-27
dc.contributor.authorCan, Geylani
dc.contributor.authorKauerhof, Anastasia Christine
dc.contributor.authorMacak, Dominik
dc.contributor.authorZegerman, Philip
dc.contributor.orcidCan, Geylani [0000-0002-1716-7830]
dc.contributor.orcidZegerman, Philip [0000-0002-5707-1083]
dc.date.accessioned2019-01-08T00:31:01Z
dc.date.available2019-01-08T00:31:01Z
dc.date.issued2019-02-07
dc.description.abstractAcross eukaryotes, disruption of DNA replication causes an S phase checkpoint response, which regulates multiple processes, including inhibition of replication initiation and fork stabilization. How these events are coordinated remains poorly understood. Here, we show that the replicative helicase component Cdc45 targets the checkpoint kinase Rad53 to distinct replication complexes in the budding yeast Saccharomyces cerevisiae. Rad53 binds to forkhead-associated (FHA) interaction motifs in an unstructured loop region of Cdc45, which is phosphorylated by Rad53 itself, and this interaction is necessary for the inhibition of origin firing through Sld3. Cdc45 also recruits Rad53 to stalled replication forks, which we demonstrate is important for the response to replication stress. Finally, we show that a Cdc45 mutation found in patients with Meier-Gorlin syndrome disrupts the functional interaction with Rad53 in yeast. Together, we present a single mechanism by which a checkpoint kinase targets replication initiation and elongation complexes, which may be relevant to human disease.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.34919
dc.identifier.eissn1097-4164
dc.identifier.issn1097-2765
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287607
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.molcel.2018.11.025
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCdc45
dc.subjectDNA damage
dc.subjectDNA replication
dc.subjectRad53
dc.subjectbudding yeast
dc.subjectcheckpoint
dc.subjectreplisome
dc.subjectCell Cycle Proteins
dc.subjectCheckpoint Kinase 2
dc.subjectCongenital Microtia
dc.subjectDNA Damage
dc.subjectDNA Repair
dc.subjectDNA Replication
dc.subjectDNA, Fungal
dc.subjectDNA-Binding Proteins
dc.subjectGrowth Disorders
dc.subjectHumans
dc.subjectMicrognathism
dc.subjectMutation
dc.subjectNuclear Proteins
dc.subjectPatella
dc.subjectPhosphorylation
dc.subjectProtein Binding
dc.subjectS Phase Cell Cycle Checkpoints
dc.subjectSaccharomyces cerevisiae
dc.subjectSaccharomyces cerevisiae Proteins
dc.titleHelicase Subunit Cdc45 Targets the Checkpoint Kinase Rad53 to Both Replication Initiation and Elongation Complexes after Fork Stalling.
dc.typeArticle
dcterms.dateAccepted2018-11-15
prism.endingPage573.e3
prism.issueIdentifier3
prism.publicationDate2019
prism.publicationNameMol Cell
prism.startingPage562
prism.volume73
pubs.funder-project-idWorldwide Cancer Research (formerly AICR) (10-0908)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idWellcome Trust (107056/Z/15/Z)
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)
pubs.funder-project-idCancer Research Uk (None)
rioxxterms.licenseref.startdate2019-02
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.molcel.2018.11.025

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
1-s2.0-S109727651830995X-main.pdf
Size:
4.24 MB
Format:
Adobe Portable Document Format
Description:
Published version
Licence
https://creativecommons.org/licenses/by/4.0/
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
DepositLicenceAgreementv2.1.pdf
Size:
150.9 KB
Format:
Adobe Portable Document Format
Download

Collections

Cambridge University Research Outputs