A5019478811- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Genomics and Chromatin Dynamics
- Carcinogens and Genotoxicity Assessment
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Cancer Research and Treatments
- Computational Drug Discovery Methods
- Liver physiology and pathology
- Mitochondrial Function and Pathology
- 14-3-3 protein interactions
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Enzyme Structure and Function
- Genetics and Neurodevelopmental Disorders
- Nuclear Receptors and Signaling
- Telomeres, Telomerase, and Senescence
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Protein Kinase Regulation and GTPase Signaling
University of Geneva
2016-2025
University Hospital of Geneva
2023
NBE Therapeutics (Switzerland)
2022
Biomedical Research Foundation of the Academy of Athens
2017
Niigata University
2013
University of Padua
2013
Service de la Santé Publique
2013
Institute for Molecular Medicine Finland
2012
University of Helsinki
2012
National and Kapodistrian University of Athens
2008-2012
p53 binding protein 1 (53BP1), a proposed to function as transcriptional coactivator of the tumor suppressor, has BRCT domains with high homology Saccharomyces cerevisiae Rad9p DNA damage checkpoint protein. To examine whether 53BP1 role in cellular response damage, we probed its intracellular localization by immunofluorescence. In untreated primary cells and U2OS osteosarcoma cells, exhibited diffuse nuclear staining; whereas, within 5-15 min after exposure ionizing radiation (IR),...
Chk2/hcds1, the human homolog of Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after damage. Like its yeast homologs, Chk2/hCds1 phosphorylates Cdc25C in vitro, suggesting it arrests cells G(2) response to We expressed analyzed their cell cycle profile. Wild-type, but not catalytically inactive, led G(1) arrest The was inhibited by cotransfection dominant-negative p53 mutant,...
The p53 tumor suppressor protein is a sequence-specific transcription factor that modulates the response of cells to DNA damage. Recent studies suggest full transcriptional activity requires coactivators CREB binding (CBP)/p300 and PCAF. These interact with each other, both possess intrinsic histone acetyltransferase activity. Furthermore, p300 acetylates activate its in vitro. In this study, we demonstrate PCAF also vitro at lysine residue distinct from acetylated by thereby increases p53's...
Stabilization of p53 in response to DNA damage is caused by its dissociation from Mdm2, a protein that targets for degradation the proteasome. Dissociation Mdm2 could be damage-induced posttranslational modifications. The ATM and ATR kinases, whose activation ionizing radiation (IR) UV light, respectively, required stabilization, directly phosphorylate on Ser-15. However, phosphorylation Ser-15 critical apoptotic activity not stabilization. Thus, whether any modifications, which, underlie...
In budding yeast, one-ended DNA double-strand breaks (DSBs) and damaged replication forks are repaired by break-induced (BIR), a homologous recombination pathway that requires the Pol32 subunit of polymerase delta. stress is prevalent in cancer, but BIR has not been characterized mammals. cyclin E overexpression model stress, POLD3, human ortholog POL32, was required for cell cycle progression processive synthesis. Segmental genomic duplications induced were also dependent on as BIR-mediated...
Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced (BIR) for damaged forks. To better understand BIR, we performed a targeted siRNA screen genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, gene dispensable normal development in mice, among top hits. In cells which fork collapse induced oncogenes or chemicals, Rad52 protein...
Abstract An important advance in cancer therapy has been the development of poly(ADP-ribose) polymerase (PARP) inhibitors for treatment homologous recombination (HR)-deficient cancers 1–6 . PARP trap PARPs on DNA. The trapped are thought to block replisome progression, leading formation DNA double-strand breaks that require HR repair 7 Here we show PARP1 functions together with TIMELESS and TIPIN protect early S phase from transcription–replication conflicts. Furthermore, synthetic lethality...
Abstract The accurate execution of DNA replication requires a strict control the licensing factors hCdt1 and hCdc6. role these key molecules in carcinogenesis has not been clarified. To examine how early during cancer development deregulation occurs, we investigated their status epithelial lesions covering progressive stages hyperplasia, dysplasia, full malignancy, mostly from same patients. Abnormal accumulation both proteins occurred stage dysplasia. A frequent cause unregulated hCdc6...