A5089156584- Cancer therapeutics and mechanisms
- DNA and Nucleic Acid Chemistry
- Bioactive Compounds and Antitumor Agents
- Lung Cancer Research Studies
- DNA Repair Mechanisms
- Advanced biosensing and bioanalysis techniques
- Synthesis and Biological Evaluation
- Neutropenia and Cancer Infections
- Antibiotics Pharmacokinetics and Efficacy
- Polyomavirus and related diseases
- Synthesis and biological activity
- RNA Interference and Gene Delivery
- Synthesis and bioactivity of alkaloids
- RNA and protein synthesis mechanisms
- Natural Compounds in Disease Treatment
- Neuroblastoma Research and Treatments
- RNA modifications and cancer
- Cancer Treatment and Pharmacology
- Metal complexes synthesis and properties
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Acute Myeloid Leukemia Research
- Molecular Biology Techniques and Applications
- interferon and immune responses
University of Bologna
2016-2025
Policlinico S.Orsola-Malpighi
2013
Shanghai Institute of Materia Medica
2012
Chinese Academy of Sciences
2012
State Key Laboratory of Drug Research
2012
National Cancer Institute
1990-2009
University of Maryland, Baltimore County
2004
St. Jude Children's Research Hospital
2004
Menarini Group (Italy)
1999-2002
Fondazione IRCCS Istituto Nazionale dei Tumori
1992-2001
G quadruplexes (G4s) and R loops are noncanonical DNA structures that can regulate basic nuclear processes trigger damage, genome instability, cell killing. By different technical approaches, we here establish specific G4 ligands stabilize G4s simultaneously increase R-loop levels within minutes in human cancer cells. Genome-wide mapping of showed the studied likely cause spreading to adjacent regions containing structures, preferentially at 3′-end expressed genes, which partially...
In order to investigate the mechanism of topoisomerase I inhibition by camptothecin, we studied induction DNA cleavage purified mammalian in a series oligonucleotides and analyzed sequence locations preferred sites SV40 genome. The were derived from major camptothecin-induced site (Jaxel, C., Kohn, K. W., Pommier, Y. (1988) Nucleic Acids Res. 16, 11157 11170) with cleaved bond their center. length was critical since detectable only 30 20 base pair-(bp) oligonucleotides, but not 12-bp...
MiR-519d belongs to the chromosome 19 miRNA cluster (C19MC), largest human cluster. One of its members, miR-519d, is over-expressed in hepatocellular carcinoma (HCC) and we characterized contribution hepatocarcinogenesis. In HCC cells, over-expression miR-519d promotes cell proliferation, invasion impairs apoptosis following anticancer treatments. These functions are, at least part, exerted through direct targeting CDKN1A/p21, PTEN, AKT3 TIMP2. The mechanisms underlying aberrant expression...
Doxorubicin, a DNA-intercalator, is one of several anti-cancer drugs that have been found to stabilizes topoisomerase II cleavage complexes at drug-specific DNA sites. The distribution and sequence environments doxorubicin-stabillzed sites were determined in the SV40 genome. be most concentrated major nuclear matrix-associated region nearly absent vicinity replication origin including enhancer sequences 21 -bp 72-bp tandem repeats. Among 97 doxorubicin-stabilized localized level, none...
Although accumulation of DNA damage and genomic instability in resting cells can cause neurodegenerative disorders, our understanding how transcription produces double-strand breaks (DSBs) is limited. Transcription-blocking topoisomerase I cleavage complexes (TOP1ccs) are frequent events that prime DSB production non-replicating cells. Here, we report a mechanism their formation by showing they arise from two nearby single-strand (SSBs) on opposing strands: one SSB the removal...
Co-transcriptional R-loops are abundant non-B DNA structures in mammalian genomes. Topoisomerase I (Top1) is often thought to regulate R-loop formation owing its ability resolve both positive and negative supercoils. How Top1 regulates at a global level unknown. Here, we perform high-resolution strand-specific mapping human cells depleted for find that depletion results gains losses thousands of transcribed loci, delineating two distinct gene classes. characteristic long, highly transcribed,...
Background and Methodology Recently, we reported on a new class of naphthoquinone derivatives showing promising anti-trypanosomatid profile in cell-based experiments. The lead this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED50 80 nM against Trypanosoma brucei rhodesiense, selectivity index 74 with respect to mammalian cells. A multitarget for compound is easily conceivable, because quinones, as natural products, serve plants potent defense chemicals intrinsic multifunctional...
DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, forms a transient intermediate, I–DNA cleavage complex (Top1cc) allow strand rotation and duplex relaxation, which lead elevated levels of DNA-RNA hybrids micronuclei. To comprehend the underlying mechanisms, we have integrated genomic data Top1cc-triggered double-strand breaks (DSBs) shortly after Top1cc induction, revealing that Top1ccs increase hybrid with different mechanisms. DSBs are at highly...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSequence-selective topoisomerase II inhibition by anthracycline derivatives in SV40 DNA: relationship with DNA binding affinity and cytotoxicityGiovanni Capranico, Franco Zunino, Kurt W. Kohn, Yves PommierCite this: Biochemistry 1990, 29, 2, 562–569Publication Date (Print):January 16, 1990Publication History Published online1 May 2002Published inissue 16 January...
The effect of cyanomorpholinyldoxorubicin, morpholinyldoxorubicin, doxorubicin, and Actinomycin D were studied on purified mouse leukemia (L1210) DNA topoisomerases I II. unwinding cross-linking also studied. It was found that 1) (but not doxorubicin) stimulated topoisomerase I-induced cleavage at specific sites; 2) only doxorubicin by II; 3) higher drug concentrations, intercalators suppressed enzyme-mediated induced I, as well 4) cyanomorpholinyldoxorubicin produced DNA-DNA cross-links; no...
Several classes of antitumor drugs are known to stabilize topoisomerase complexes in which the enzyme is covalently bound a terminus DNA strand break. The cleavage sites generally different for each class drugs. We have determined sequence locations large number drugstimulated II, and find that results provide clue possible structure origin drug-specific differences. Cleavage enhancements by VM-26 amsacrine ( m -AMSA), representative II inhibitors, strong dependence on bases directly at...
Abstract Triptolide is a bioactive ingredient in traditional Chinese medicine that exhibits diverse biologic properties, including anticancer properties. Among its many putative targets, this compound has been reported to bind XPB, the largest subunit of general transcription factor TFIIH, and cause degradation Rpb1 RNA polymerase II (RNAPII). In study, we clarify multiple important questions concerning significance basis for triptolide action at core target. decreased levels cancer cells...
Whole transcriptome analyses have revealed new classes of long ncRNA (lncRNA), the functions which are however largely unknown. Recently, we showed that antitumor DNA topoisomerase I (Top1) inhibitor camptothecin (CPT) increases cellular levels two antisense lncRNAs at 5' (5'aHIF-1α) and 3' (3'aHIF-1α) ends human HIF-1α gene. To gain insights into their functions, here determined structural functional aspects RNAs in cancer cell lines kidney tumor specimen. We found transcripts activated...
Abstract DNA Topoisomerase I (Top1) is required to relax supercoils generated by RNA polymerases (RNAPs). Top1 inhibited with high specificity camptothecin (CPT), an effective anticancer agent, and oxidative base damage ribonucleotides in strands, resulting into Top1-DNA cleavage complexes (Top1ccs). To understand how Top1ccs affect genome stability, we have investigated the global transcriptional response CPT-induced Top1ccs. trigger accumulation of antisense RNAPII transcripts specifically...
The human KRAS transcript contains a G-rich 5'-UTR sequence (77% GC) harboring several G4 motifs capable to form stable RNA G-quadruplex (RG4) structures that can serve as targets for small molecules. A biotin-streptavidin pull-down assay showed 4,11-bis(2-aminoethylamino)anthra[2,3-b]furan-5,10-dione (2a) binds RG4s in the under low-abundance cellular conditions. Dual-luciferase assays demonstrated 2a and its analogue 4,11-bis(2-aminoethylamino)anthra[2,3-b]thiophene-5,10-dione (2b) repress...