A5014033014- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- Plant Genetic and Mutation Studies
- Photosynthetic Processes and Mechanisms
- Carcinogens and Genotoxicity Assessment
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Plant Disease Resistance and Genetics
- Bacterial Genetics and Biotechnology
- Fungal Infections and Studies
- Mitochondrial Function and Pathology
- Cancer therapeutics and mechanisms
- Genetic Neurodegenerative Diseases
- PARP inhibition in cancer therapy
- Chromosomal and Genetic Variations
- Nuclear Structure and Function
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Plant Pathogens and Fungal Diseases
- Synthesis and Biological Activity
- Glycosylation and Glycoproteins Research
Istituto di Genetica Molecolare
2012-2024
National Research Council
2024
IFOM
2005-2021
Istituto Nazionale di Fisica Nucleare, Sezione di Pavia
2014
University of Milan
2000-2010
Brandeis University
2005
Institute of Molecular Biology and Pathology
2001
Transcription hinders replication fork progression and stability. The ATR checkpoint specialized DNA helicases assist synthesis across transcription units to protect genome integrity. Combining genomic genetic approaches together with the analysis of intermediates, we searched for factors coordinating transcription. We show that Sen1/Senataxin DNA/RNA helicase associates forks, promoting their RNA polymerase II (RNAPII)-transcribed genes. sen1 mutants accumulate aberrant structures DNA-RNA...
S-phase cells overcome chromosome lesions through replication-coupled recombination processes that seem to be assisted by recombination-dependent DNA structures and/or replication-related sister chromatid junctions. RecQ helicases, including yeast Sgs1 and human BLM, have been implicated in both replication protect genome integrity preventing unscheduled mitotic events. We studied the helicase-mediated mechanisms controlling stability analyzing forks encountering a damaged template sgs1...
The cytotoxic activity of ecteinascidin 743 (ET-743), a natural product derived from the marine tunicate Ecteinascidia turbinata that exhibits potent anti-tumor in pre-clinical systems and promising phase I II clinical trials, was investigated number cell with well-defined deficiencies DNA-repair mechanisms. ET-743 binds to N2 guanine minor groove, but its does not appear be related DNA-topoisomerase poisoning as drug is equally active wild-type yeast deletion gene. Defects mismatch repair...
Uncoordinated clashes between replication forks and transcription cause stress genome instability, which are hallmarks of cancer neurodegeneration. Here, we investigate the outcomes head-on replication-transcription collisions, using as a model system budding yeast mutants for helicase Sen1, ortholog human Senataxin. We found that RNA Polymerase II accumulates together with RNA:DNA hybrids at sites collisions. The fork both arrested during clash, leading to DNA damage and, in long run,...
The yeast DNA polymerase ␣-primase B subunit functions in initiation of replication.This protein is present two forms, 86 and 91 kDa, the p91 polypeptide results from cell cycle-regulated phosphorylation p86.The G 1 arises by dephosphorylation while cells are exiting mitosis, becomes phosphorylated early S phase, competent sufficient to initiate replication.The transiently synthesized as a consequence periodic transcription POL12 gene no earlier than 2 .Phosphorylation does not require...
Mutations in the genes encoding BLM and WRN RecQ DNA helicases MRE11-RAD50-NBS1 complex lead to genome instability cancer predisposition syndromes. The Saccharomyces cerevisiae Sgs1 helicase Mre11 protein, together with Srs2 helicase, prevent chromosome rearrangements are implicated damage checkpoint response recombination. By searching for physical interactors, we have identified Mre11. We show that Srs2, Sgs1, form a large complex, likely yet unidentified proteins. This reorganizes into...
Cdk1 kinase phosphorylates budding yeast Srs2, a member of UvrD protein family, displays both DNA translocation and unwinding activities in vitro. Srs2 prevents homologous recombination by dismantling Rad51 filaments is also required for double-strand break (DSB) repair. Here we examine the biological significance Cdk1-dependent phosphorylation using mutants that constitutively express phosphorylated or unphosphorylated isoforms. We found targets to repair DSB and, particular, complete...
An important but still enigmatic function of DNA:RNA hybrids is their role in DNA double-strand break (DSB) repair. Here, we show that Sen1, the budding yeast ortholog human helicase Senataxin, recruited at an HO endonuclease-induced DSB and limits local accumulation hybrids. In absence hybrid proximal to promotes increased binding Ku70-80 (KU) complex site, mutagenic non-homologous end joining (NHEJ), micro-homology-mediated (MMEJ), chromosome translocations. We also homology-directed...
Abstract Senataxin is an evolutionarily conserved DNA/RNA helicase, whose dysfunctions are linked to neurodegeneration and cancer. A main activity of this protein the removal R-loops, which nucleic acid structures capable promote DNA damage replication stress. Here we found that deficiency causes release damaged into extranuclear bodies, called micronuclei, triggering massive recruitment cGAS, apical sensor innate immunity pathway, downstream stimulation interferon genes. Such cGAS-positive...