A5082983471- DNA Repair Mechanisms
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Advanced Proteomics Techniques and Applications
- RNA Research and Splicing
- Cancer therapeutics and mechanisms
- PARP inhibition in cancer therapy
- Microbial Metabolic Engineering and Bioproduction
- DNA and Nucleic Acid Chemistry
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Cancer, Hypoxia, and Metabolism
- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Polyomavirus and related diseases
- HIV-related health complications and treatments
- SARS-CoV-2 detection and testing
- Neuroscience and Neuropharmacology Research
- Bariatric Surgery and Outcomes
- Acute Lymphoblastic Leukemia research
Norwegian University of Science and Technology
2015-2025
Central Norway Regional Health Authority
2013-2024
University of Oslo
2024
Oslo University Hospital
2024
St Olav's University Hospital
2019-2021
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2015
Joint BioEnergy Institute
2014
Google (United States)
2008
Max Planck Institute of Molecular Cell Biology and Genetics
2005
Universidade de Brasília
2005
Numerous proteins, many essential for the DNA replication machinery, interact with proliferating cell nuclear antigen (PCNA) through PCNA-interacting peptide (PIP) sequence called PIP box. We have previously shown that oxidative demethylase human AlkB homologue 2 (hABH2) colocalizes PCNA in foci. In this study, we show hABH2 interacts a posttranslationally modified via novel motif, which term motif (APIM). identify APIM >200 other proteins involved maintenance, transcription, and...
The most common mutations in cancer are C to T transitions, but their origin has remained elusive. Recently, mutational signatures of APOBEC-family cytosine deaminases were identified many cancers, suggesting off-target deamination uracil as a mutagenic mechanism. Here we present evidence from mass spectrometric quantitation deoxyuridine DNA that shows significantly higher genomic content B-cell lymphoma cell lines compared non-lymphoma and normal circulating lymphocytes. levels highly...
Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is most commonly chemotherapeutic agent against myeloma. However, despite a 70–80% initial response rate, virtually all patients eventually relapse due to emergence drug-resistant tumour cells. By using global proteomic transcriptomic profiling on melphalan sensitive resistant RPMI8226 cell lines followed by...
The order of enzymatic activity across Golgi cisternae is essential for complex molecule biosynthesis. However, an inability to separate has meant that the cisternal distribution most resident proteins, and their underlying localization mechanisms, are unknown. Here, we exploit differences in surface charge intact perform separation early late subcompartments. We determine protein glycan abundance profiles Golgi; over 390 proteins identified, including 136 new additions, with 180...
More than 170 post-transcriptional RNA modifications regulate the localization, processing and function of cellular RNAs, aberrant have been linked to a range human diseases. The modification landscape in atherosclerosis, main underlying cause cardiovascular diseases, is still largely unknown.We used mass spectrometry analyse selection RNA-modifying enzymes N6-methyladenosine (m6A) carotid atherosclerotic lesion samples representing early advanced stages atherosclerosis as compared...
Abstract The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated various combinations and HDACi MS275 (Entinostat), subsequently assessed for viability, cycle changes, genotoxic markers....
To aid in debugging efforts to increase yield, titer, and productivity of engineered metabolic pathways, computational models are increasingly needed predict how changes experimentally manipulable variables such as enzyme expression map pathway flux. Here, an ordinary differential equation model is developed for a heterologous mevalonate E. coli using kinetic parameters culled from literature concentrations derived Selective Reaction Monitoring Mass Spectrometry (SRM-MS). identify most...
Recessive loss of function the neuronal ubiquitin hydrolase UCHL1 has been implicated in early-onset progressive neurodegeneration (MIM no. 615491), so far only one family. In this study a second family is characterized, and functional consequences identified mutations are explored. Three siblings developed childhood-onset optic atrophy, followed by spasticity ataxia. Whole exome sequencing compound heterozygous variants UCHL1, c.533G > A (p.Arg178Gln) c.647C (p.Ala216Asp), cosegregating...
Human AlkB homologues ABH2 and ABH3 repair 1-methyladenine 3-methylcytosine in DNA/RNA by oxidative demethylation. The enzymes have similar overall folds active sites, but are functionally divergent. efficiently demethylates both single- double-stranded (ds) DNA, whereas has a strong preference for single-stranded DNA RNA. We find that divergent F1 β-hairpins proximity of the sites central substrate specificities. Swapping hairpins between resulted hybrid proteins resembling donor proteins....
Alterations in checkpoint and DNA repair pathways may provide adaptive mechanisms contributing to acquired drug resistance. Here, we investigated the levels of proteins mediating damage signaling -repair RPMI8226 multiple myeloma cells its Melphalan-resistant derivative 8226-LR5. We observed markedly reduced steady-state glycosylases UNG2, NEIL1 MPG resistant cross-resistance agents inducing their respective base lesions. Conversely, alkali-labile sites was apparently enhanced cells, as...
Base lesions in DNA can stall the replication machinery or induce mutations if bypassed. Consequently, must be repaired before a post-replicative process to maintain genomic stability. excision repair (BER) is main pathway for of base and known associated with replication, but how BER organized during unclear. Here we coupled iPOND (isolation proteins on nascent DNA) technique targeted mass-spectrometry analysis, which enabled us detect all required monitor their spatiotemporal orchestration...
UNG is the major uracil-DNA glycosylase in mammalian cells and involved both error-free base excision repair of genomic uracil mutagenic uracil-processing at antibody genes. However, regulation these different processes currently not well understood. The gene encodes two isoforms, UNG1 UNG2, each possessing unique N-termini that mediate translocation to mitochondria nucleus, respectively. A strict subcellular localization isoform has been widely accepted despite a lack models study them...
Oxidation resistance gene 1 (OXR1) protects cells against oxidative stress. We find that male mice with brain-specific isoform A knockout (Oxr1A-/-) develop fatty liver. RNA sequencing of Oxr1A-/- liver indicates decreased growth hormone (GH) signaling, which is known to affect metabolism. Indeed, Gh expression reduced in pituitary gland and rat adenoma cell-line GH3. show fasting-blood GH levels. Pull-down proximity ligation assays reveal OXR1A associated arginine methyl transferase PRMT5....
The NTHL1 and NEIL1-3 DNA glycosylases are major enzymes in the removal of oxidative base lesions, via excision repair (BER) pathway. It is expected that lack these activities would render cells vulnerable to stress, promoting cell death. Intriguingly, we found single, double, triple, quadruple glycosylase knockout HAP1 are, however, more resistant stress caused by genotoxic agents than wild type cells. Furthermore, glutathione depletion NEIL deficient further enhances resistance death...
Using a combination of tandem mass spectrometric sequencing and sequence similarity searches, we characterized the larvae venom moth Cerodirphia speciosa, which belongs to Saturniidae family Lepidoptera order. Despite paucity available database resources, approach enabled us identify 48 out 58 attempted spots on its two-dimensional gel electrophoresis map, represented 37 unique proteins, whereas it was only possible 13 proteins by conventional non-error tolerant searching methods. The...
Polyphenols are a class of natural compounds whose potential as antioxidant, anti-inflammatory, and anti-angiogenesis has been reported in many pathological conditions. Red raspberry extract, rich polyphenols, to exert anti-inflammatory effects prevent cell proliferation distinct animal models. However, the signaling pathways involved remain unknown. Herein, we used human microvascular endothelial cells (HMVECs) determine influence red phenolic compound extract concentrations, ranging from...
Oxidation Resistance 1 (OXR1) gene is a highly conserved of the TLDc domain-containing family. OXR1 involved in fundamental biological and cellular processes, including DNA damage response, antioxidant pathways, cell cycle, neuronal protection, arginine methylation. In 2019, five patients from three families carrying four biallelic loss-of-function variants were reported to be associated with cerebellar atrophy. However, impact on functions molecular mechanisms human brain largely unknown....