A5079714249- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Click Chemistry and Applications
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Photosynthetic Processes and Mechanisms
- PARP inhibition in cancer therapy
- RNA modifications and cancer
University Hospital Bonn
2019-2025
University of Bologna
2016-2018
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...
Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA RNA in vitro, however a systems-wide analysis of DHX36 targets function is lacking. We map globally binding to human cell lines find it preferentially interacting with G-rich G4-forming sequences more than 4500 mRNAs. While knockout (KO) results significant increase target abundance, ribosome...
G-Quadruplex-binding compounds are currently perceived as possible anticancer therapeutics. Here, starting from a promising lead, small series of novel hydrazone-based were synthesized and evaluated G-quadruplex binders. The in vitro G-quadruplex-binding properties the investigated employing both human telomeric oncogene promoter G-quadruplexes with different folding topologies targets. present investigation led to identification potent stabilizers high selectivity over duplex DNA preference...
Abstract Nucleic acids can fold into G-quadruplex (G4) structures that fine-tune biological processes. Proteins are required to recognize G4 and coordinate their function. Here we identify Zuo1 as a novel G4-binding protein in vitro vivo. In vivo the absence of fewer form, cell growth slows cells become UV sensitive. Subsequent experiments reveal these cellular changes due reduced levels structures. function at results recruitment nucleotide excision repair (NER) factors, which has positive...
Abstract Accurate DNA replication is essential for genomic stability and cancer prevention. Homologous recombination important high-fidelity damage tolerance during replication. How the homologous machinery recruited to intermediates unknown. Here, we provide evidence that a Rad51 paralog-containing complex, budding yeast Shu directly recognizes enables of predominantly lagging strand abasic sites. We show complex becomes chromatin associated when cells accumulate sites S phase. also...
Abstract Senescence has two roles in oncology: it is known as a potent tumor-suppressive mechanism, which also supports tissue regeneration and repair, to contribute reduced patient resilience, might lead cancer recurrence resistance after therapy. can be activated DNA damage-dependent -independent manner. It not clear type of genomic lesions induces senescence, but that UV irradiation activate cellular senescence photoaged skin. Proteins support the repair damage are linked how they still...
Homologous recombination (HR) is important for DNA damage tolerance during replication. The yeast Shu complex, a conserved homologous factor, prevents replication-associated mutagenesis. Here we examine how cells require the complex coping with MMS-induced lesions We find that Csm2, subunit of binds to autonomous-replicating sequences (ARS) in yeast. Further evolutionary studies reveal and human complexes have co-evolved specific replication-initiation factors. connection between replication...
Nucleic acids can fold into non-canonical secondary structures named G-quadruplexes (G4s), which consist of guanine-rich sequences stacked guanine tetrads stabilized by Hoogsteen hydrogen bonding, π-π interactions, and monovalent cations. G4 structure formation properties are well established in vitro, but potential vivo functions remain controversial. G4s evolutionarily enriched at distinct, functional genomic loci, both genetic molecular findings indicate that involved multiple aspects...
Abstract Background SARS-CoV-2 infection depends on the host cell factors angiotensin-converting enzyme 2, ACE2, and transmembrane serinprotease TMPRSS2. Potential inhibitors of these proteins would be ideal targets against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Our data opens possibility that changes within TMPRSS2 can modulate outcome during a Results We reveal acts not only viral entry but has also an important role replication. In addition to...
G-Quadruplexes (G4s) and R-loops are non-B DNA structures that can regulate transcription replication. G4s formed from four guanine residues held together in the same plane by Hoogsteen hydrogen bonds further stabilized presence of monovalent cations. triple-strand contain an RNA-DNA hybrid displaced single-stranded DNA. One most important features influence these is GC content. Indeed, R-loop be favoured a high density non-template strand this specifically due to higher thermodynamic...
Abstract G-quadruplexes (G4s) and R-loops are non-B DNA structures that can regulate basic processes such as transcription replication. Unscheduled formation of is regarded highly deleterious to cells, R loops induce replicative stress damage leading genome instability. G4s formed by four guanine residues held together Hoogsteen hydrogen bonds stabilized monovalent cations. triple-stranded contain an RNA-DNA hybrid duplex a displaced single-stranded DNA. We have recently shown Topoisomerase...