A5063928729- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Carcinogens and Genotoxicity Assessment
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Vector-Borne Animal Diseases
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- T-cell and Retrovirus Studies
- Herpesvirus Infections and Treatments
- Folate and B Vitamins Research
- Organophosphorus compounds synthesis
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
ETH Zurich
2016-2024
University of Bern
2014-2015
To examine the effect of torsional constraints imposed on DNA substrates Cas9 cleavage, we prepared constrained using a origami frame. By fixing dsDNA at connectors frame, created torsionally or relaxed substrates. We quantified cleavage and by with qPCR. Moreover, observed Cas9/sgRNA complex bound to characterized dissociation high-speed atomic force microscopy. The results revealed that nontarget strand reduced efficiency drastically, whereas target had little cleavage. present study...
By replicating damaged nucleotides, error-prone DNA translesion synthesis (TLS) enables the completion of replication, albeit at expense fidelity. TLS helix-distorting lesions, that usually have reduced capacity basepairing, comprises insertion opposite lesion followed by extension, latter in particular polymerase ζ (Pol ζ). However, little is known about involvement Pol non- or poorly-distorting, but miscoding, lesions such as O
An adenosine analog devoid of the N3-nitrogen purine ring was incorporated into catalytic cores well-known DNA enzymes 8–17 and 10–23. The results show that minor groove interactions are important for activity thus constitute an feature enzymes.
The generation of chemical alkylating agents from nitrosation glycine and bile acid conjugates in the gastrointestinal tract is hypothesized to initiate carcinogenesis. O(6)-carboxymethylguanine (O(6)-CMG) a product DNA alkylation derived nitrosated glycine. Although tendency structurally related adduct O(6)-methylguanine code for misincoporation TTP during replication well-established, impact presence O(6)-CMG template on efficiency fidelity translesion synthesis (TLS) by human polymerases...
ConspectusChemical damage to DNA is a key initiator of adverse biological consequences due disruption the faithful reading genetic code. For example, O6-alkylguanine (O6-alkylG) adducts are strongly miscoding during replication when damaged nucleobase template for polymerase-mediated translesion synthesis. Thus, mutations derived from O6-alkylG can have severe effects on protein translation and function an early event in initiation carcinogenesis. However, low abundance these places...
Carboxymethylation of DNA, including the formation DNA adduct O6-carboxymethylguanine (O6-CMG), is associated with lifestyle factors, such as diet. It can impede replicative polymerases (Pols) and lead to replication fork stalling, or an alternative means for proceed by translesion synthesis (TLS). TLS requires specialized Pols characterized open preformed active sites capable preferential bypass alkylated adducts but that have high error rates, leading mutations. Human O6-CMG varying...
O6-Alkylguanine DNA adducts are repaired by the suicide enzyme alkylguanine alkyltransferase (AGT). AGT facilitates repair binding in minor groove, flipping out damaged base, and transferring O6-alkyl group to a cysteine residue enzyme's active site. Despite there being significant knowledge concerning mechanism of repair, is limited insight regarding how altered interactions adduct with its complementary base duplex influence recognition repair. In this study, relationship pairing human...
The traditional strategy for the introduction of chemical functionalities is use solid-phase synthesis by appending suitably modified phosphoramidite precursors to nascent chain. However, conditions used during and restriction rather short sequences hamper applicability this methodology. On other hand, nucleoside triphosphates are activated building blocks that have been employed mild numerous functional groups into nucleic acids, a paves way acids in wide-ranging palette practical...
Chemically induced DNA lesions can become replication substrates that are bypassed by low-fidelity polymerases. Following nucleotide misinsertion opposite a lesion, the extension step contribute to preserving such errors and lead genomic instability cancer. polymerase ζ, B-family polymerase, is proficient as an extender catalyzes elongation; however, chemical factors impact its not understood. This study addresses question of how ζ achieves examining ability recombinant human extend from...
Repair of airway epithelium after viral infection involves migration epithelial cells to cover injured, denuded areas. We determined whether reduces the capability bronchial migrate and attach extracellular matrix proteins. Inoculation bovine in vitro with herpesvirus-1 reduced their ability two different assays cell migration. When attachment were performed, fewer attached both control wells protein-precoated wells, suggesting that general mechanisms adherence substrates altered by...
The traditional strategy for the introduction of chemical functionalities is use solid-phase synthesis by appending suitably modified phosphoramidite precursors to nascent chain. However, conditions used during and restriction rather short sequences hamper applicability this methodology. On other hand, nucleoside triphosphates are activated building blocks that have been employed mild numerous functional groups into nucleic acids, a paves way acids in wide-ranging palette practical...