A5073295537- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Carcinogens and Genotoxicity Assessment
- Bacterial Genetics and Biotechnology
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- SARS-CoV-2 detection and testing
- Biosensors and Analytical Detection
- RNA Research and Splicing
- Plant Genetic and Mutation Studies
- Pharmaceutical and Antibiotic Environmental Impacts
- Genomics and Chromatin Dynamics
- Cancer Research and Treatments
- Cytomegalovirus and herpesvirus research
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Protist diversity and phylogeny
- DNA and Biological Computing
Weizmann Institute of Science
2015-2024
American Committee for the Weizmann Institute of Science
2019
Technion – Israel Institute of Technology
2012-2015
Ben-Gurion University of the Negev
2012-2014
Rambam Health Care Campus
2012-2013
Sheba Medical Center
2012-2013
Carmel Medical Center
2012-2013
Clalit Health Services
2012-2013
New York University
2009-2011
Leiden University Medical Center
2011
BackgroundAn Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility limitations for SARS-CoV-2 diagnosis.MethodsSerology from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, an in-house RBD ELISA were included. Negative samples 2391 individuals representative the population, 698 PCR positive patients, collected between March May 2020, analyzedFindingsImmunoassays sensitivities 81.5%-89.4%...
Replication of DNA lesions leads to the formation mutations. In Escherichia coli this process is regulated by SOS stress response, and requires mutagenesis proteins UmuC UmuD′. Analysis translesion replication using a recently reconstituted in vitro system (Reuven, N. B., Tomer, G., Livneh, Z. (1998) Mol. Cell 2, 191–199) revealed that lesion bypass occurred with fusion protein, UmuD′, RecA, SSB absence added polymerase. Further analysis was polymerase (E. V), weak polymerizing activity....
The unique properties of DNA make it a fundamental building block in the fields supramolecular chemistry, nanotechnology, nano-circuits, molecular switches, devices, and computing. In our recently introduced autonomous automaton, molecules serve as input, output, software, hardware consists restriction ligation enzymes using ATP fuel. addition to information, stores energy, available on hybridization complementary strands or hydrolysis its phosphodiester backbone. Here we show that single...
Replication across unrepaired DNA lesions in mammalian cells is effected primarily by specialized, low fidelity polymerases. We studied translesion synthesis (TLS) a benzo[a]pyrene-guanine (BP-G) adduct, major mutagenic lesion generated tobacco smoke. This was done using quantitative assay that measures TLS indirectly, measuring the recovery of gapped plasmids transfected into cultured cells. Analysis PolK(+/+) mouse embryo fibroblasts (MEFs) showed BP-G adduct occurred with an efficiency 48...
Translesion DNA synthesis (TLS) is a damage tolerance mechanism in which specialized low-fidelity polymerases bypass replication-blocking lesions, and it usually associated with mutagenesis. In Saccharomyces cerevisiae key event TLS the monoubiquitination of PCNA, enables recruitment to damaged site through their ubiquitin-binding domain. mammals, however, there debate on requirement for ubiquitinated PCNA (PCNA-Ub) TLS. We show that UV-induced Rpa foci, indicative single-stranded (ssDNA)...
The p53 tumor suppressor that plays a central role in the cellular response to genotoxic stress was suggested be associated with DNA repair machinery which mostly involves nucleotide excision (NER). In present study we show for first time is also directly involved base (BER). These experiments were performed temperature‐sensitive (ts) mutants previously studied vivo experimental models. We report here ts can acquire wild‐type activity under vitro conditions. Using of murine and human origin,...
Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out polymerase η, the POLH gene product. A deficiency in η due to germ-line mutations causes hereditary disease xeroderma pigmentosum variant ( XPV ), which is characterized sunlight sensitivity and extreme predisposition sunlight-induced skin cancer. are UV hypermutable activity of mutagenic TLS across CPD, explains cancer patients. However, identity backup that carries this was...
Translesion DNA synthesis (TLS) employs low-fidelity polymerases to bypass replication-blocking lesions, and being associated with chromosomal replication was presumed occur in the S phase of cell cycle. Using immunostaining anti-replication protein A antibodies, we show that UV-irradiated mammalian cells, single-stranded gaps formed during persist into G2 cycle, where their repair is completed depending on polymerase ζ Rev1. Analysis TLS using a high-resolution gapped-plasmid assay system...
The Y family DNA polymerase Rev1 has been proposed to play a regulatory role in the replication of damaged templates.To elucidate mechanism by which promotes damage bypass, we have analyzed progression on UV light-damaged mouse embryonic fibroblasts that contain defined deletion N-terminal BRCT domain or are deficient for Rev1.We provide evidence plays coordinating two modes i.e., an early and late pathway.The cells carrying pathway, reflecting mutagenic translesion synthesis.Rev1-deficient...
Abstract Background Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property p21 WAF1/Cip1 , showing that chronic expression in p53-deficient environment causes genomic by deregulation replication licensing machinery. Results We now demonstrate can further fuel suppressing repair capacity low- high-fidelity pathways deal...
When challenged by DNA-damaging agents, Escherichia coli cells respond inducing the SOS stress response, which leads to an increase in mutation frequency two mechanisms: translesion replication, a process that causes mutations because of misinsertion opposite lesions, and inducible mutator activity, acts at undamaged sites. Here we report DNA polymerase V (pol V; UmuC), previously has been shown be lesion-bypass polymerase, was highly mutagenic during vitro gap-filling replication gapped...
Mutations in oncogenes and tumor suppressor genes are critical the development of cancer. A major pathway for formation mutations is replication unrepaired DNA lesions. To better understand mechanism translesion (TLR) mammals, a quantitative assay TLR cultured cells was developed. The based on transient transfection with gapped plasmid, carrying site-specific lesion gap region. Filling by assayed subsequent bioassay, ability plasmid extracted from cells, to transform an Escherichia coli...
Abstract An increasing number of studies indicate that reduced DNA-repair capacity is associated with increased cancer risk. Using a functional assay for the removal oxidative DNA lesion 8-oxoguanine by enzyme glycosylase 1 (OGG1), we have previously shown OGG activity risk factor in lung cancer. Here, report peripheral blood mononuclear cells from 37 cases squamous cell carcinoma head and neck (SCCHN) was significantly lower than 93 control subjects, frequency matched age gender. Retesting...
Purpose: To measure the yield of DNA strand breaks and clustered lesions in plasmid irradiated with protons, helium nuclei, γ-rays.Materials methods: Plasmid was 1.03, 19.3 249 MeV protons (linear energy transfer = 25.5, 2.7, 0.39 keV μm – 1 respectively), 26 nuclei (25.5 μm) γ-rays (137Cs or 60Co) phosphate buffer containing 2 mM 200 glycerol. Single-and double-strand (SSB DSB) were measured by gel electrophoresis, base quantified converting them into irreparable DSB transformed...
Abstract Cells cope with replication-blocking lesions via translesion DNA synthesis (TLS). TLS is carried out by low-fidelity polymerases that replicate across lesions, thereby preventing genome instability at the cost of increased point mutations. Here we perform a two-stage siRNA-based functional screen for mammalian genes and identify 17 validated genes. One genes, NPM1 , frequently mutated in acute myeloid leukaemia (AML). We show (nucleophosmin) regulates interaction catalytic core...