Publicaties

This optimized protocol (including links to instruction videos) describes a comet-based in vitro DNA repair assay that is relatively simple, versatile, and inexpensive, enabling the detection of base and nucleotide excision repair activity. Protein extracts from samples are incubated with agarose-embedded substrate nucleoids ('naked' supercoiled DNA) containing specifically induced DNA lesions (e.g., resulting from oxidation, UVC radiation or ...

The objective of the present study was to develop a cellular phenotype assay for nucleotide excision repair (NER), using benzo[a]pyrene diol epoxide (BPDE) as model mutagen. Since in vitro exposure to BPDE may lead to DNA strand breaks resulting from both direct interaction with DNA and incisions introduced by the repair enzymes, we aimed to discriminate between both types of breaks using the comet assay and quantified the DNA strand breaks ...

Spinal cord injury is a devastating condition that affects about 21 million people worldwide, leading to severe disabilities. These injuries impact motor functions, sensory perception, autonomic processes, psychological well-being, and social interactions, significantly burdening patients, their families, and healthcare systems. Unfortunately, despite extensive research, there is no cure for spinal cord injury yet. This PhD Thesis focuses on how ...

The maintenance of genome stability is a continuous challenge for all organisms that is encountered by DNA repair mechanisms. In the human genome, the most important individual source of point mutations is spontaneous hydrolytic deamination of 5- methylcytosine (Sved and Bird, 1990; Krawczak et al., 1998; Fryxell and Moon, 2005). This results in the formation of G:T mismatches and, if not properly repaired, in C-to-T transitions after ...

Genetic information is constantly being attacked by intrinsic and extrinsic damaging agents, such as reactive oxygen species, atmospheric radiation, environmental chemicals, and chemotherapeutics. If DNA modifications persist, they can adversely affect the polymerization of DNA or RNA, leading to replication fork collapse or transcription arrest, or can serve as mutagenic templates during nucleic acid synthesis reactions. To combat the ...

In this thesis, we aimed to create specific binders for 1-methyl adenine (1mA) in methylation-damaged DNA. Such binders may have potential as biosensor of DNA methylation lesions as the current experimental state-of-the- art does not allow for in vivo detection of methylated DNA. To that end, we initiated the molecular evolution of the E. coli AlkB (EcAlkB) DNA repair protein, a prototypical and promiscuous demethylase known to preferentially ...

DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) are under investigation for the treatment of cancer, including the plasma cell malignancy multiple myeloma (MM). Evidence exists that DNA damage and repair contribute to the cytotoxicity mediated by the DNMTi decitabine. Here, we investigated the DNA damage response (DDR) induced by decitabine in MM using 4 human MM cell lines and the murine 5T33MM model. In ...

Alzheimer disease (AD) is the most prominent form of dementia and has received considerable attention due to its growing burden on economic, healthcare and basic societal infrastructures. The two major neuropathological hallmarks of AD, i.e., extracellular amyloid beta (A beta) peptide plaques and intracellular hyperphosphorylated Tau neurofibrillary tangles, have been the focus of much research, with an eye on understanding underlying disease ...