A5052214217- DNA Repair Mechanisms
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Fungal and yeast genetics research
- RNA Interference and Gene Delivery
- Telomeres, Telomerase, and Senescence
- Bacterial Genetics and Biotechnology
- Genetic Neurodegenerative Diseases
Instituto Gulbenkian de Ciência
2025
Istituto Universitario di Studi Superiori di Pavia
2017-2021
Istituto di Genetica Molecolare
2015-2021
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,...
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...
The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, sen1 mutants, when a fork clashes head-on with is arrested and, as consequence, progression sister moving opposite direction within same replicon also impaired. Therefore, remain coupled one two transcription, fate different from that experienced Double Strand Breaks. We dormant origins are activated to ensure DNA...
Patricia L. Abreu1,5, Valentina Riva1,3,5, Luca Zardoni1,4,5 and Claus M. Azzalin1,2 1GIMM - Gulbenkian Institute for Molecular Medicine, 1649-035 Lisbon, Portugal 2Faculty of University 1649-028 Correspondence: claus.azzalin{at}gimm.pt ↵3 Current address: Science Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria. ↵4 Istituto di Genetica Molecolare Luigi Cavalli-Sforza, CNR, 27100 Pavia, Italy. ↵5 These authors contributed equally to this work.