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dc.contributor.authorRausch, C
dc.contributor.authorZhang, P
dc.contributor.authorCasas-Delucchi, CS
dc.contributor.authorDaiß, JL
dc.contributor.authorEngel, C
dc.contributor.authorCoster, G
dc.contributor.authorHastert, FD
dc.contributor.authorWeber, P
dc.contributor.authorCardoso, MC
dc.date.accessioned2021-07-27T08:08:45Z
dc.date.available2021-07-27T08:08:45Z
dc.date.issued2021-06-16
dc.identifier.citationNucleic acids research, 2021
dc.identifier.issn0305-1048
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4701
dc.identifier.eissn1362-4962
dc.identifier.doi10.1093/nar/gkab509
dc.description.abstractDNA base modifications diversify the genome and are essential players in development. Yet, their influence on DNA physical properties and the ensuing effects on genome metabolism are poorly understood. Here, we focus on the interplay of cytosine modifications and DNA processes. We show by a combination of in vitro reactions with well-defined protein compositions and conditions, and in vivo experiments within the complex networks of the cell that cytosine methylation stabilizes the DNA helix, increasing its melting temperature and reducing DNA helicase and RNA/DNA polymerase speed. Oxidation of methylated cytosine, however, reverts the duplex stabilizing and genome metabolic effects to the level of unmodified cytosine. We detect this effect with DNA replication and transcription proteins originating from different species, ranging from prokaryotic and viral to the eukaryotic yeast and mammalian proteins. Accordingly, lack of cytosine methylation increases replication fork speed by enhancing DNA helicase unwinding speed in cells. We further validate that this cannot simply be explained by altered global DNA decondensation, changes in histone marks or chromatin structure and accessibility. We propose that the variegated deposition of cytosine modifications along the genome regulates DNA helix stability, thereby providing an elementary mechanism for local fine-tuning of DNA metabolism.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleCytosine base modifications regulate DNA duplex stability and metabolism.
dc.typeJournal Article
dcterms.dateAccepted2021-06-03
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1093/nar/gkab509
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-06-16
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNucleic acids research
pubs.notesNo embargo
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/Genome Replication
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/Genome Replication
pubs.publication-statusPublished
pubs.embargo.termsNo embargo
icr.researchteamGenome Replication
icr.researchteamGenome Replicationen_US
dc.contributor.icrauthorCoster, Gideonen


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