A5012585842- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Systemic Lupus Erythematosus Research
- Cytokine Signaling Pathways and Interactions
- Carcinogens and Genotoxicity Assessment
- Genetics and Neurodevelopmental Disorders
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- Circular RNAs in diseases
- melanin and skin pigmentation
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Bacterial Genetics and Biotechnology
- Polyomavirus and related diseases
- MicroRNA in disease regulation
- Rheumatoid Arthritis Research and Therapies
- RNA Interference and Gene Delivery
- Developmental Biology and Gene Regulation
- Plant Genetic and Mutation Studies
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
Alexander Fleming Biomedical Sciences Research Center
2010-2024
Leiden University Medical Center
2006-2011
Leiden University
2005
University of Sussex
2000-2004
Aristotle University of Thessaloniki
1993
Heterochromatin protein 1 (HP1) family members are chromatin-associated proteins involved in transcription, replication, and chromatin organization. We show that HP1 isoforms HP1-α, HP1-β, HP1-γ recruited to ultraviolet (UV)-induced DNA damage double-strand breaks (DSBs) human cells. This response requires the chromo shadow domain of is independent H3K9 trimethylation detect UV DSBs. Loss results high sensitivity light ionizing radiation nematode Caenorhabditis elegans, indicating essential...
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...
Synovial fibroblasts (SFs) are specialized cells of the synovium that provide nutrients and lubricants for proper function diarthrodial joints. Recent evidence appreciates contribution SF heterogeneity in arthritic pathologies. However, normal profiles molecular networks govern transition from homeostatic to remain poorly defined.
Transcription-coupled nucleotide excision repair (TC-NER) allows RNA polymerase II (RNAPII)-blocking lesions to be rapidly removed from the transcribed strand of active genes. Defective TCR in humans is associated with Cockayne syndrome (CS), typically caused by defects either CSA or CSB. Here, we show that CSB contains a ubiquitin-binding domain (UBD). Cells expressing UBD-less (CSB(del)) have phenotypes similar those cells lacking CSB, but these can suppressed appending heterologous UBD,...
Complex molecular responses preserve gene expression accuracy and genome integrity in the face of environmental perturbations. Here we report that, response to UV irradiation, RNA polymerase II (RNAPII) molecules are dynamically synchronously released from promoter-proximal regions into elongation promote uniform accelerated surveillance whole transcribed genome. The maximised influx de novo RNAPII correlates with increased damage-sensing, as confirmed by progressive accumulation at...
The rad18 gene of Schizosaccharomyces pombe is an essential that involved in several different DNA repair processes. Rad18 (Smc6) a member the structural maintenance chromosomes (SMC) family and, together with its SMC partner Spr18 (Smc5), forms core high-molecular-weight complex. We show here both S. and human Smc5 -6 interact through their hinge domains four independent temperature-sensitive mutants are all mutated at same glycine residue region. This mutation abolishes interactions...
Abstract UV-damaged DNA-binding protein (UV-DDB) is essential for global genome repair (GGR) of UV-induced cyclobutane pyrimidine dimers (CPD). Unlike human cells, rodent epidermal cells are deficient in GGR CPDs and express a subunit UV-DDB, DDB2, at low level. In this study, we generated mice (K14-DDB2) ectopically expressing mouse DDB2 elevated levels. Enhanced expression both delayed the onset squamous cell carcinoma decreased number tumors per chronically UV-B light-exposed hairless...
Nucleotide excision repair (NER) operates through coordinated assembly of factors into pre- and postincision complexes. The step NER includes gap-filling DNA synthesis ligation. However, the exact composition this NER-associated complex in vivo dynamic interactions involved are not well understood. Using immunofluorescence, chromatin immunoprecipitation, live-cell protein studies, we show that replication factor C (RFC) is implicated mammalian cells. Small interfering RNA-mediated knockdown...
Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several types have been identified based on the initiating stimulus, such as replicative (RS), stress-induced (SIS) oncogene-induced (OIS). These subtypes are heterogeneous often develop subset-specific phenotypes. Reduced protein synthesis is considered hallmark, but whether this trait pertains to various if distinct molecular mechanisms involved...
Studies based on cell-free systems and in vitro-cultured living cells support the concept that many cellular processes, such as transcription initiation, are highly dynamic: individual proteins stochastically bind to their substrates disassemble after reaction completion. This dynamic nature allows quick adaptation of changing conditions. However, it is unknown what extent this organization holds for postmitotic embedded mammalian tissue. To allow analysis initiation dynamics directly into...
Single-stranded DNA gaps that might arise by futile repair processes can lead to mutagenic events and challenge genome integrity. Nucleotide excision (NER) is an evolutionarily conserved mechanism, essential for removal of helix-distorting lesions. In the currently prevailing model, NER operates through coordinated assembly factors into pre- post-incision complexes; however, its regulation in vivo poorly understood. Notably, transition from dual incision synthesis should be rigidly...
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 Inhibition of transcription caused by DNA damage-impaired RNA polymerase II (Pol II) elongation conceals a local increase in de novo transcription, slowly progressing from Transcription Start Sites (TSSs) to gene ends. Although associated with accelerated repair Pol II-encountered lesions and limited mutagenesis, it is still unclear how this mechanism maintained during genotoxic stress-recovery. Here we uncover widespread gain chromatin accessibility preservation the active H3K27ac...