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dc.contributor.authorDouglas, ME
dc.contributor.authorDiffley, JFX
dc.date.accessioned2021-08-12T08:54:30Z
dc.date.available2021-08-12T08:54:30Z
dc.date.issued2021-06-04
dc.identifier.citationNucleic acids research, 2021, 49 (10), pp. 5671 - 5683
dc.identifier.issn0305-1048
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4738
dc.identifier.eissn1362-4962
dc.identifier.doi10.1093/nar/gkab416
dc.description.abstractTelomeres are copied and reassembled each cell division cycle through a multistep process called telomere replication. Most telomeric DNA is duplicated semiconservatively during this process, but replication forks frequently pause or stall at telomeres in yeast, mouse and human cells, potentially causing chronic telomere shortening or loss in a single cell cycle. We have investigated the cause of this effect by examining the replication of telomeric templates in vitro. Using a reconstituted assay for eukaryotic DNA replication in which a complete eukaryotic replisome is assembled and activated with purified proteins, we show that budding yeast telomeric DNA is efficiently duplicated in vitro unless the telomere binding protein Rap1 is present. Rap1 acts as a roadblock that prevents replisome progression and leading strand synthesis, but also potently inhibits lagging strand telomere replication behind the fork. Both defects can be mitigated by the Pif1 helicase. Our results suggest that GC-rich sequences do not inhibit DNA replication per se, and that in the absence of accessory factors, telomere binding proteins can inhibit multiple, distinct steps in the replication process.
dc.formatPrint
dc.format.extent5671 - 5683
dc.languageeng
dc.language.isoeng
dc.publisherOXFORD UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectTelomere
dc.subjectSaccharomycetales
dc.subjectDNA Helicases
dc.subjectTelomere-Binding Proteins
dc.subjectSaccharomyces cerevisiae Proteins
dc.subjectRecombinant Proteins
dc.subjectTranscription Factors
dc.subjectDNA Replication
dc.subjectGene Expression
dc.subjectBase Composition
dc.subjectIn Vitro Techniques
dc.titleBudding yeast Rap1, but not telomeric DNA, is inhibitory for multiple stages of DNA replication in vitro.
dc.typeJournal Article
dcterms.dateAccepted2021-05-26
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1093/nar/gkab416
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNucleic acids research
pubs.issue10
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Telomere Biology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Telomere Biology
pubs.publication-statusPublished
pubs.volume49
pubs.embargo.termsNot known
icr.researchteamTelomere Biology
icr.researchteamTelomere Biology
dc.contributor.icrauthorDouglas, Maxwell


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