A5033544272- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Occupational and environmental lung diseases
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
- interferon and immune responses
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Pluripotent Stem Cells Research
- Renal and related cancers
- PI3K/AKT/mTOR signaling in cancer
- Liver physiology and pathology
- Microtubule and mitosis dynamics
- Toxin Mechanisms and Immunotoxins
- Medical Imaging and Pathology Studies
- Genetics and Neurodevelopmental Disorders
- PARP inhibition in cancer therapy
- Macrophage Migration Inhibitory Factor
- HER2/EGFR in Cancer Research
- Cancer, Hypoxia, and Metabolism
- Viral Infections and Immunology Research
- Chromosomal and Genetic Variations
University of Zurich
2015-2024
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2000-2015
IFOM
2006-2007
University of Ferrara
2001
Istituti di Ricovero e Cura a Carattere Scientifico
2001
Tecnologie Avanzate (Italy)
1998
DNA damage tolerance during eukaryotic replication is orchestrated by PCNA ubiquitination. While monoubiquitination activates mutagenic translesion synthesis, polyubiquitination an error-free pathway, elusive in mammals, enabling bypass template switching. Fork reversal driven vitro multiple enzymes, including the translocase ZRANB3, shown to bind polyubiquitinated PCNA. However, whether this interaction promotes fork remodeling and switching vivo was unknown. Here we show that...
Highlights d RNF168 mediates K27 ubiquitination of histone H2As is the major ubiquitin mark on chromatin upon DNA damage strictly required for proper activation response 53BP1, Rap80, RNF168, and RNF169 directly recognize linkage
AbstractUbiquitination of histones plays a critical role in the regulation several processes within nucleus, including maintenance genome stability and transcriptional regulation. The only known ubiquitination site on is represented by conserved Lys residue located at C terminus protein. Here, we describe novel ubiquitin mark N-terminal tail histone H2As consisting two residues positions 13 15 (K13/K15). This “bidentate” target DNA damage response (DDR) ligases RNF8 RNF168. Histone mutants...
Recent studies suggested that simian virus 40 (SV40) may cause malignant mesothelioma, although the pathogenic mechanism is unclear. We found in SV40-positive mesothelioma cells, hepatocyte growth factor (HGF) receptor (Met) was activated. In human mesothelial cells (HMC) transfected with full-length SV40 DNA (SV40-HMC), Met activation associated S-phase entry, acquisition of a fibroblastoid morphology, and assembly viral particles. Coculture experiments revealed ability SV40-HMC to infect...
Ubiquitin is a highly versatile post-translational modification that controls virtually all types of cellular events. Over the past ten years we have learned diverse forms ubiquitin modifications and binding modules co-exist in cell, giving rise to complex networks protein:protein interactions. A central problem continues puzzle ubiquitinologists how cells translate this myriad stimuli into specific responses. This classical signalling problem. Here, draw parallels with phosphorylation...
Abstract Background Modulation of chromatin structure has emerged as a critical molecular device to control gene expression. Histones undergo different post-translational modifications that increase accessibility number regulatory factors. Among them, histone ubiquitination appears relevant in nuclear processes govern silencing, either by inhibiting or activating transcription, and maintain genome stability, acting scaffold properly organize the DNA damage response. Thus, it is paramount...
DNA replication is highly regulated by the ubiquitin system, which plays key roles upon stress. The ubiquitin-like modifier ISG15 (interferon-stimulated gene 15) induced interferons, bacterial and viral infection, damage, but it also constitutively expressed in many types of cancer, although its role tumorigenesis still largely elusive. Here, we show that localizes at forks, complex with PCNA nascent DNA, where regulates synthesis. Indeed, high levels ISG15, intrinsic or interferon-β,...
Summary High plasma levels of nicotinamide phosphoribosyltransferase ( NAMPT ), traditionally considered an intracellular enzyme with a key role in NAD synthesis, have been reported several oncological, inflammatory and metabolic diseases. We now show that e can be actively released by melanoma cells vitro. analysed the mechanisms its release, we found both classical non‐classical pathway involvement. cells, our hands, has paracrine autocrine effects: it activates MAPK , AKT NF ‐ κ B...
Ubiquitination regulates important cellular processes, including the DNA damage response (DDR) and repair. The complexity of ubiquitin-mediated signals is decoded by ubiquitin receptors, which contain protein modules named binding domains (UBDs). We previously identified a new ligase, RNF168, involved in DDR endowed with two UBDs MIU (motif interacting ubiquitin). Here we have provided identification novel UBD, UMI (UIM- MIU-related UBD), present characterized interaction surface ubiquitin,...
Recent discoveries have highlighted the importance of Haspin kinase activity for correct positioning Aurora B at centromere. phosphorylates Thr(3) histone H3 (H3), which provides a signal to localize centromere mitotic chromosomes. To date, is only confirmed substrate. We used combination biochemical, pharmacological, and mass spectrometric approaches study consequences inhibition in cells. quantified 3964 phosphorylation sites on chromatin-associated proteins identified protein-protein...
Macrophage Stimulating Protein (MSP), a serum factor related to Hepatocyte Growth Factor, was originally discovered stimulate chemotaxis of murine resident peritoneal macrophages. MSP is the ligand for Ron, member Met subfamily tyrosine kinase receptors. The effects on human macrophages and role played in pathophysiology have long been elusive. We show here that recombinant (hrMSP) evokes dose‐dependent superoxide anion production alveolar as well monocyte‐derived macrophages, but not...
Abstract Global-genome nucleotide excision repair (GG-NER) prevents ultraviolet (UV) light-induced skin cancer by removing mutagenic cyclobutane pyrimidine dimers (CPDs). These lesions are formed abundantly on DNA wrapped around histone octamers in nucleosomes, but a specialized damage sensor known as DDB2 ensures that they accessed the XPC initiator of GG-NER activity. We report promotes CPD recruiting methyltransferase ASH1L, which methylates lysine 4 H3. In turn, methylated H3 facilitates...
Abstract DNA replication and repair defects or genotoxic treatments trigger interferon (IFN)-mediated inflammatory responses. However, whether how IFN signaling in turn impacts the process has remained elusive. Here we show that basal levels of IFN-stimulated gene 15, ISG15, its conjugation (ISGylation) are essential to protect nascent from degradation. Moreover, IFNβ treatment restores fork stability BRCA1/2-deficient cells, which strictly depends on topoisomerase-1, rescues lethality...
Ron, the tyrosine kinase receptor for macrophage-stimulating protein is responsible proliferation and migration of cells from different tissues. Ron can acquire oncogenic potential by single point mutations in domain, dysregulated signaling has been involved development human cancers. We have previously shown that ligand-activated recruits negative regulator c-Cbl, which mediates its ubiquitylation degradation. Here we report ubiquitylated also U-box E3 ligase C-terminal Hsc70-interacting...
Abstract Loss of function BRCA1-associated protein 1 (BAP1) is observed in about 50% malignant pleural mesothelioma (MPM) cases. The aim this study was to investigate whether aspect could be exploited for targeted therapy. A genetically engineered model established expressing either functional or nonfunctional BAP1, and whole-genome siRNA synthetic lethality screens were performed assessing differentially impaired survival between the two cell lines. screen unexpectedly revealed 11 hits (FDR...
Despite vaccination and screening measures, anogenital cancer, mainly promoted by HPV16 oncoproteins, still represents the fourth tumor second cause of death among women. Cell replication fidelity is result host DNA damage response (DDR). Unlike many viruses that promote their life cycle through DDR inactivation, HR-HPVs encourage cells proliferation despite turned on. Why how it occurs has been only partially elucidated. During infection, E6 links degrades p53 via binding to E6AP LXXLL...