- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Bladder and Urothelial Cancer Treatments
- Cancer Research and Treatments
- Skin Protection and Aging
- Dietary Effects on Health
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Circadian rhythm and melatonin
- Molecular Biology Techniques and Applications
- Diet and metabolism studies
- Genomics, phytochemicals, and oxidative stress
- Mosquito-borne diseases and control
- Polyamine Metabolism and Applications
- DNA and Nucleic Acid Chemistry
- Amino Acid Enzymes and Metabolism
- Gene expression and cancer classification
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Viral Infections and Vectors
- RNA regulation and disease
National Institute for Public Health and the Environment
2014-2023
National Institute of Public Health
2001-2023
Leiden University Medical Center
2009-2020
Erasmus MC
2014
Utrecht University
1980-2010
The University of Texas MD Anderson Cancer Center
2010
University of Houston
2010
University of Alabama at Birmingham
2010
Appalachian Fruit Research Laboratory
2008
United States Department of Agriculture
2008
One of the factors postulated to drive aging process is accumulation DNA damage. Here, we provide strong support for this hypothesis by describing studies mice with a mutation in XPD , gene encoding helicase that functions both repair and transcription mutated human disorder trichothiodystrophy (TTD). TTD were found exhibit many symptoms premature aging, including osteoporosis kyphosis, osteosclerosis, early greying, cachexia, infertility, reduced life-span. carrying an additional XPA which...
Cockayne syndrome (CS) is a photosensitive, DNA repair disorder associated with progeria that caused by defect in the transcription-coupled subpathway of nucleotide excision (NER). Here, complete inactivation NER Csb(m/m)/Xpa(-/-) mutants causes phenotype reliably mimics human progeroid CS syndrome. Newborn mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis several...
Mutant dwarf and calorie-restricted mice benefit from healthy aging unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between genome-wide liver expression profiles of with those two extremes Contrary to expectation, find significant, associations long-lived mice. Subsequent analysis significantly over-represented biological processes...
The immunostimulatory cytokine IL-12 is able to antagonize immunosuppression induced by solar/ultraviolet (UV) radiation via yet unknown mechanisms. was recently found induce deoxyribonucleic acid (DNA) repair. UV-induced DNA damage an important molecular trigger for UV-mediated immunosuppression. Thus, we initiated studies into immune restoration discern whether its effects are linked prevented both suppression of the induction contact hypersensitivity and depletion Langerhans cells,...
Defects in the DNA repair mechanism nucleotide excision (NER) may lead to tumors xeroderma pigmentosum (XP) or premature aging with loss of subcutaneous fat Cockayne syndrome (CS). Mutations mitochondrial (mt)DNA play a role aging, but link between NER-associated CS proteins and base (BER)-associated remains enigmatic. We show functional increase CSA CSB inside mt complex formation mtDNA, human 8-oxoguanine glycosylase (mtOGG)-1, single-stranded binding protein (mtSSBP)-1 upon oxidative...
Abstract DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined lesions cells and tissues without simultaneously damaging other biomolecules cellular structures. Here we directly test whether highly toxic double-strand breaks (DSBs) alone can drive an ageing phenotype using adenovirus-based system based on tetracycline-controlled expression SacI restriction enzyme. We deliver adenovirus mice compare...
Homologous recombination is a versatile DNA damage repair pathway requiring Rad51 and Rad54. Here we show that mammalian Rad54 paralog, Rad54B, displays physical functional interactions with are similar to those of While ablation in mouse embryonic stem (ES) cells leads mild reduction homologous efficiency, the absence Rad54B has little effect. However, both dramatically reduces efficiency. Furthermore, protects ES from ionizing radiation interstrand cross-linking agent mitomycin C....
We have previously reported the isolation of gene coding for a 25‐kDa polypeptide present in purified yeast QH 2 :cytochrome c oxidoreductase preparation, which was thus identified as Rieske ironsulphur protein [Van Loon et al. (1983) Gene 26 , 261–272]. Subsequent DNA sequence analysis here reveals, however, that encoded is fact manganese superoxide dismutase, mitochondrial matrix protein. Comparison with known amino acid mature indicates it synthesized an N‐terminal extension 27 acids. In...