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New Findings on Antisense Technology Described by Investigators at CASPUR

February 13, 2014



By a News Reporter-Staff News Editor at Gene Therapy Weekly -- New research on Biotechnology is the subject of a report. According to news originating from Rome, Italy, by NewsRx correspondents, research stated, "DNA 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)."

Our news journalists obtained a quote from the research from CASPUR, "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."

According to the news editors, the research concluded: "The results clarify molecular features of a response pathway leading to transcription-dependent genome instability and altered transcription regulation."

For more information on this research see: Antisense transcripts enhanced by camptothecin at divergent CpG-island promoters associated with bursts of topoisomerase I-DNA cleavage complex and R-loop formation. Nucleic Acids Research, 2013;41(22):10110-10123. Nucleic Acids Research can be contacted at: Oxford Univ Press, Great Clarendon St, Oxford OX2 6DP, England. (Oxford University Press - www.oup.com/; Nucleic Acids Research - nar.oxfordjournals.org)

The news correspondents report that additional information may be obtained from J. Marinello, CASPUR, I-00185 Rome, Italy. Additional authors for this research include G. Chillemi, S. Bueno, S.G. Manzo and G. Capranico (see also Biotechnology).

Keywords for this news article include: Rome, Antisense Technology, Biotechnology, Italy, Europe, DNA Research, Topoisomerase, Bioengineering, Enzymes and Coenzymes

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Source: Gene Therapy Weekly


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