Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/47391
DC FieldValueLanguage
dc.contributor.authorMarinello, Jessicait
dc.contributor.authorChillemi, Giovanniit
dc.contributor.authorBueno, Susanait
dc.contributor.authorManzo, Stefano Git
dc.contributor.authorCapranico, Giovanniit
dc.date.accessioned2022-03-28T17:56:41Z-
dc.date.available2022-03-28T17:56:41Z-
dc.date.issued2013it
dc.identifier.issn0305-1048it
dc.identifier.urihttp://hdl.handle.net/2067/47391-
dc.description.abstractDNA Topoisomerase I (Top1) is required to relax DNA supercoils generated by RNA polymerases (RNAPs). Top1 is inhibited with high specificity by camptothecin (CPT), an effective anticancer agent, and by oxidative base damage and ribonucleotides in DNA strands, resulting into Top1-DNA cleavage complexes (Top1ccs). To understand how Top1ccs affect genome stability, we have investigated the global transcriptional response to CPT-induced Top1ccs. Top1ccs trigger an accumulation of antisense RNAPII transcripts specifically at active divergent CpG-island promoters in a replication-independent and Top1-dependent manner. As CPT increases antisense transcript levels in the presence of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a transcription inhibitor, Top1ccs likely impair antisense RNA degradation. Time-course data showed a burst of Top1ccs increased by CPT at promoter sites and along transcribed regions, causing a transient block of RNAPII at the promoter. Moreover, cell immunofluorescence analyses showed that Top1ccs induce a transient increase of R-loops specifically at highly transcribed regions such as nucleoli in a Top1-dependent manner. Thus, a specific and highly dynamic transcriptional response to Top1ccs occurs at divergent active CpG-island promoters, which may include a transient stabilization of R-loops. The results clarify molecular features of a response pathway leading to transcription-dependent genome instability and altered transcription regulation.it
dc.format.mediumSTAMPAit
dc.language.isoengit
dc.titleAntisense transcripts enhanced by camptothecin at divergent CpG-island promoters associated with bursts of topoisomerase I-DNA cleavage complex and R-loop formationit
dc.typearticle*
dc.identifier.doi10.1093/nar/gkt778it
dc.identifier.pmid23999093it
dc.identifier.scopus2-s2.0-84890411532it
dc.identifier.urlhttps://dspace.unitus.it/handle/2067/30243it
dc.relation.journalNUCLEIC ACIDS RESEARCHit
dc.relation.firstpage10110-23it
dc.relation.lastpage10123it
dc.relation.volume41it
dc.relation.issue22it
dc.subject.scientificsectorLS2_12 Bioinformaticsit
dc.subject.ercsectorAGR/17it
dc.description.internationalnoit
dc.contributor.countryITAit
dc.type.refereeREF_1it
dc.type.miur262*
item.fulltextWith Fulltext-
item.openairetypearticle-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.journal.journalissn0305-1048-
crisitem.journal.anceE122791-
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