A5009758630- Acute Lymphoblastic Leukemia research
- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Chronic Lymphocytic Leukemia Research
- PARP inhibition in cancer therapy
- Education, Psychology, and Social Research
- Retinoids in leukemia and cellular processes
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Lymphoma Diagnosis and Treatment
- interferon and immune responses
- Nanoparticle-Based Drug Delivery
- Nanocluster Synthesis and Applications
- Gold and Silver Nanoparticles Synthesis and Applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Research and Treatments
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Cell death mechanisms and regulation
- Cancer therapeutics and mechanisms
- FOXO transcription factor regulation
- RNA and protein synthesis mechanisms
- Integrated Circuits and Semiconductor Failure Analysis
Czech Academy of Sciences, Institute of Molecular Genetics
2009-2024
University of Sussex
2016
Institute of Molecular Genetics
2013
Czech Academy of Sciences
2013
Charles University
2005-2009
Many cancers arise at sites of infection and inflammation. Cellular senescence, a permanent state cell cycle arrest that provides barrier against tumorigenesis, is accompanied by elevated proinflammatory cytokines such as IL1, IL6, IL8 TNFα. Here we demonstrate media conditioned cells undergoing any the three main forms i.e. replicative, oncogene- drug-induced, contain high levels TGFb capable inducing reactive oxygen species (ROS)-mediated DNA damage response (DDR). Persistent cytokine...
A critical step of DNA single-strand break repair is the rapid recruitment scaffold protein XRCC1 that interacts with, stabilizes and stimulates multiple enzymatic components process. promoted by PARP1, an enzyme activated following damage synthesizes ADP-ribose polymers binds directly. However, cells possess two other strand break-induced PARP enzymes, PARP2 PARP3, for which roles are unclear. To address their involvement in endogenous into oxidized chromatin we have established 'isogenic'...
Cytolethal distending toxins (CDTs) are proteins produced and secreted by facultative pathogenic strains of Gram-negative bacteria with potentially genotoxic effects. Mammalian cells exposed to CDTs undergo cell type-dependent cell-cycle arrest or apoptosis; however, the fate responses such intoxication mechanistically incompletely understood. Here we show that both normal cancer (BJ, IMR-90 WI-38 fibroblasts, HeLa U2-OS lines) survive acute phase Haemophilus ducreyi CDT possess hallmarks...
Cells are constantly challenged by DNA damage and protect their genome integrity activation of an evolutionary conserved response pathway (DDR). A central core DDR is composed a spatiotemporally ordered net post-translational modifications, among which protein phosphorylation plays major role. Activation checkpoint kinases ATM/ATR Chk1/2 leads to temporal arrest in cell cycle progression (checkpoint) allows time for repair. Following repair, cells re-enter the recovery. Wip1 phosphatase...
Abstract Neurodegeneration is a common hallmark of individuals with hereditary defects in DNA single-strand break repair; process regulated by poly(ADP-ribose) metabolism. Recently, mutations the ARH3 (ADPRHL2) hydrolase that removes ADP-ribose from proteins have been associated neurodegenerative disease. Here, we show -mutated patient cells accumulate mono(ADP-ribose) scars on core histones are molecular memory recently repaired breaks. We demonstrate chromatin result reduced endogenous...
The Promyelocytic leukemia protein (PML) tumor suppressor is upregulated in several forms of cellular senescence, however the mechanism its induction elusive. Here we show that genotoxic drugs induce such as 5-bromo-2'deoxyuridine (BrdU), thymidine (TMD), distamycin A (DMA), aphidicolin (APH), etoposide (ET) and camptothecin (CPT) all evoke expansion PML nuclear compartment association with persistent DNA lesions human cancer cell lines normal diploid fibroblasts. This phenomenon was...
Abstract Mutations in BRAT1 , encoding BRCA1-associated ATM activator 1, have been associated with neurodevelopmental and neurodegenerative disorders characterized by heterogeneous phenotypes varying levels of clinical severity. However, the underlying molecular mechanisms disease pathology remain poorly understood. Here, we show that tightly interacts INTS9/INTS11 subunits Integrator complex processes 3’ ends various noncoding RNAs pre-mRNAs. We find functions are disrupted deletion. In...
In response to DNA damage, the histone PARylation factor 1 (HPF1) regulates PARP1/2 activity, facilitating serine ADP-ribosylation of chromatin-associated factors. While are known for their role in single-strand break repair (SSBR), significance HPF1 this process remains unclear. Here, we investigated impact deficiency on cellular survival and SSBR following exposure various genotoxins. We found that loss did not generally increase sensitivity agents typically induce breaks (SSBs) repaired...
Tumor suppressor PML is induced under viral and genotoxic stresses by interferons JAK-STAT signaling. However, the mechanism responsible for its cell type-specific regulation non-stimulated conditions poorly understood. To analyze variation of expression, we utilized three human types, BJ fibroblasts HeLa U2OS lines, each with a distinct expression pattern. Analysis signaling in lines revealed differences levels activated STAT3 but not STAT1 correlating mRNA protein levels. RNAi-mediated...
Cationic colloidal gold nanorods (GNRs) have a great potential as theranostic tool for diverse medical applications. GNRs' properties such cellular internalization and stability are determined by physicochemical characteristics of their surface coating. GNRs modified (16-mercaptohexadecyl)trimethylammonium bromide (MTAB), MTABGNRs, show excellent uptake. Despite promise biomedicine, however, relatively little is known about the pathways that facilitate uptake GNRs, subcellular fate...
MRD based on leukemia-specific immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements has become a tool influencing clinical decisions in many therapeutic trials for childhood acute lymphoblastic leukemia (ALL). It been repeatedly documented, that positive pre-transplant is highly predictive post-transplant relapse of ALL, but we have failed to document the same value 14 children with Ph+ALL which at our unit underwent allogeneic stem cell transplantation (SCT). The presence...