FACT Is a Sensor of DNA Torsional Stress in Eukaryotic Cells

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dc.contributor.authorSafina, A.en_US
dc.contributor.authorCheney, P.en_US
dc.contributor.authorPal, M.en_US
dc.contributor.authorBrodsky, L.en_US
dc.contributor.authorIvanov, A.en_US
dc.contributor.authorKirsanov, K.en_US
dc.contributor.authorLesovaya, E.en_US
dc.contributor.authorNaberezhnov, D.en_US
dc.contributor.authorNesher, E.en_US
dc.contributor.authorKoman, I.en_US
dc.contributor.authorWang, D.en_US
dc.contributor.authorWang, J.en_US
dc.contributor.authorYakubovskaya, M.en_US
dc.contributor.authorWinkler, Duane D.en_US
dc.contributor.authorGurova, K.en_US
dc.contributor.utdAuthorWinkler, Duane D.en_US
dc.date.accessioned2018-09-24T15:55:06Z
dc.date.available2018-09-24T15:55:06Z
dc.date.created2017-01-13en_US
dc.date.issued2018-09-24
dc.descriptionIncludes supplementary materialen_US
dc.description.abstractTransitions of B-DNA to alternative DNA structures (ADS) can be triggered by negative torsional strain, which occurs during replication and transcription, and may lead to genomic instability. However, how ADS are recognized in cells is unclear. We found that the binding of candidate anticancer drug, curaxin, to cellular DNA results in uncoiling of nucleosomal DNA, accumulation of negative supercoiling and conversion of multiple regions of genomic DNA into left-handed Z-form. Histone chaperone FACT binds rapidly to the same regions via the SSRP1 subunit in curaxin-treated cells. In vitro binding of purified SSRP1 or its isolated CID domain to a methylated DNA fragment containing alternating purine/pyrimidines, which is prone to Z-DNA transition, is much stronger than to other types of DNA. We propose that FACT can recognize and bind Z-DNA or DNA in transition from a B to Z form. Binding of FACT to these genomic regions triggers a p53 response. Furthermore, FACT has been shown to bind to other types of ADS through a different structural domain, which also leads to p53 activation. Thus, we propose that FACT acts as a sensor of ADS formation in cells. Recognition of ADS by FACT followed by a p53 response may explain the role of FACT in DNA damage prevention. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.identifier.bibliographicCitationSafina, A., P. Cheney, M. Pal, L. Brodsky, et al. 2017. "FACT is a sensor of DNA torsional stress in eukaryotic cells." Nucleic Acids Research 45(4), doi:10.1093/nar/gkw1366en_US
dc.identifier.issn1362-4962en_US
dc.identifier.issue4en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6135
dc.identifier.volume45en_US
dc.language.isoenen_US
dc.relation.urihttp://dx.doi.org/10.1093/nar/gkw1366
dc.rightsCC BY-NC 4.0/ (Attribution-NonCommercial)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en_US
dc.sourceNucleic Acids Research
dc.subjectChromatinen_US
dc.subjectDNAen_US
dc.subjectDNA-Binding Proteinsen_US
dc.subjectNucleosomesen_US
dc.subjectProtein Bindingen_US
dc.subjectProtein Subunitsen_US
dc.subjectTranscription Factorsen_US
dc.subjectModels, Biologicalen_US
dc.subjectCell Lineen_US
dc.subjectChromatin Assembly and Disassemblyen_US
dc.subjectEukaryotic Cellsen_US
dc.subjectGeneticsen_US
dc.subjectHumansen_US
dc.subjectMetabolismen_US
dc.subjectChromosomal Proteins, Non-Histoneen_US
dc.titleFACT Is a Sensor of DNA Torsional Stress in Eukaryotic Cellsen_US
dc.type.genrearticleen_US

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