A5083122927- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Connective tissue disorders research
- Aortic aneurysm repair treatments
- Aortic Disease and Treatment Approaches
- Carcinogens and Genotoxicity Assessment
- PARP inhibition in cancer therapy
- Plant Genetic and Mutation Studies
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Radiation Therapy and Dosimetry
- Effects of Radiation Exposure
- Advanced Fluorescence Microscopy Techniques
- BRCA gene mutations in cancer
- Genetics, Aging, and Longevity in Model Organisms
- Cardiac Imaging and Diagnostics
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Mitochondrial Function and Pathology
- Cell Image Analysis Techniques
- Tissue Engineering and Regenerative Medicine
- Telomeres, Telomerase, and Senescence
- Photoacoustic and Ultrasonic Imaging
- Microtubule and mitosis dynamics
- Elasticity and Material Modeling
- Cardiomyopathy and Myosin Studies
Erasmus MC
2016-2025
Oncode Institute
1998-2025
Erasmus MC Cancer Institute
2020-2025
Cancer Genomics Centre
2008-2025
Erasmus University Rotterdam
2013-2024
University Medical Center
2023
Rotterdam University of Applied Sciences
2019
German Centre for Cardiovascular Research
2017
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2017
Comenius University Bratislava
2017
Interactions between ends from different DNA double-strand breaks (DSBs) can produce tumorigenic chromosome translocations. Two theories for the juxta-position of DSBs in translocations, static “contact-first” and dynamic “breakage-first” theory, differ fundamentally their requirement DSB mobility. To determine whether or not DSB-containing domains are mobile interact, we introduced linear tracks nuclei. We observed changes track morphology within minutes after induction, indicating movement...
The DNA polymerase processivity factor proliferating cell nuclear antigen (PCNA) is central to both replication and repair. ring-shaped homotrimeric PCNA encircles slides along double-stranded DNA, acting as a "sliding clamp" that localizes proteins DNA. We determined the behavior of green fluorescent protein-tagged human (GFP-hPCNA) in living cells analyze its different engagements Photobleaching tracking foci revealed dynamic equilibrium between two kinetic pools PCNA, i.e., bound free...
Rationale: Aging represents a major risk factor for coronary artery disease and aortic aneurysm formation. MicroRNAs (miRs) have emerged as key regulators of biological processes, but their role in age-associated vascular pathologies is unknown. Objective: We aim to identify miRs the vasculature that are regulated by age play age-induced pathologies. Methods Results: Expression profiling tissue young versus old mice identified several miRs. Among significantly miRs, increased expression...
Defective homologous recombination (HR) DNA repair imposed by BRCA1 or BRCA2 deficiency sensitizes cells to poly (ADP-ribose) polymerase (PARP)-1 inhibition and is currently exploited in clinical treatment of HR-deficient tumors. Here we show that mild hyperthermia (41–42.5 °C) induces degradation inhibits HR. We demonstrate can be used sensitize innately HR-proficient tumor PARP-1 inhibitors this effect enhanced heat shock protein inhibition. Our results, obtained from cell lines vivo...
Cell segmentation and tracking in time-lapse fluorescence microscopy images is a task of fundamental importance many biological studies on cell migration proliferation. In recent years, level sets have been shown to provide very appropriate framework for this purpose, as they are well suited capture topological changes occurring during mitosis, easily extend higher dimensional image data. This model evolution approach has also extended deal with cells concurrently. Notwithstanding its high...
We show here that the radiosensitive Chinese hamster cell mutant (V-C8) of group XRCC11 is defective in breast cancer susceptibility gene Brca2. The very complex phenotype V-C8 cells complemented by a single human chromosome 13 providing BRCA2 gene, as well murine Brca2 gene. deficiency causes hypersensitivity to various DNA-damaging agents with an extreme sensitivity toward interstrand DNA cross-linking agents. Furthermore, radioresistant synthesis after ionizing radiation, suggesting...
Abstract This paper considers the statistical complexities that arise due to outcome related drop‐outs in longitudinal clinical trials of randomized parallel groups design with fixed assessment times and an explanatory aim. The shortcomings currently popular methods coping problem are discussed. It is proposed progress can be made by applying modern methodology was primarily developed for sample surveys non‐response observational studies. A practical application using Hamilton Rating Scale...
Mus81-Eme1 endonuclease has been implicated in the rescue of stalled replication forks and resolution meiotic recombination intermediates yeast. We used gene targeting to study physiological requirements Mus81 mammals. Mus81-/- mice are viable fertile, which indicates that mammalian is not essential for processes associated with meiosis. Mus81-deficient cells were hypersensitive DNA cross-linking agent mitomycin C but gamma-irradiation. Remarkably, both homozygous heterozygous Mus81+/-...
Male and female germ cells can transmit genetic defects that lead to pregnancy loss, infant mortality, birth defects, diseases in offspring; however, the parental origins of transmitted are not random, with de novo mutations chromosomal structural aberrations predominantly by sperm. We tested hypotheses paternal mutagenic exposure during late spermatogenesis induce damage persists fertilizing sperm risk embryos paternally depends on efficiency maternal DNA repair first cycle after...
Live cell studies of DNA repair mechanisms are greatly enhanced by new developments in real-time visualization factors living cells. Combined with recent advances local sub-nuclear damage induction procedures these methods have yielded detailed information on the dynamics recognition and repair. Here we analyze discuss various types induced cells three different methods: pulsed 800 nm laser irradiation, Hoechst 33342 treatment combined 405 irradiation UV-C (266 nm) irradiation. A wide...
The Fibulins are a 6-member protein family hypothesized to function as intermolecular bridges that stabilize the organization of extracellular matrix structures. Here, we show reduced expression Fibulin-4 leads aneurysm formation, dissection aortic wall and cardiac abnormalities. knockdown mice with hypomorphic allele arose from targeted disruption adjacent Mus81 endonuclease gene. Mice homozygous for (Fibulin-4 R/R ) dilatation ascending aorta tortuous stiffened aorta, resulting...
Telomere maintenance and DNA repair are important processes that protect the genome against instability. mRtel1, an essential helicase, is a dominant factor setting telomere length in mice. In addition, mRtel1 involved double-strand break repair. The role of stability poorly understood. Therefore we used mRtel1-deficient mouse embryonic stem cells to examine function replication, repair, recombination, maintenance. showed sensitivity range DNA-damaging agents, highlighting its replication...
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....