Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
| Autor: | Marco Saponaro, Amaya Alzu, Daniele Piccini, Rodrigo Bermejo, Chiara Lucca, Marco Foiani, Walter Carotenuto, Alessandra Brambati, Giordano Liberi, Martina Begnis, Andrea Cocito |
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| Rok vydání: | 2012 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins Transcription Genetic Eukaryotic DNA replication RNA polymerase II Saccharomyces cerevisiae Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Control of chromosome duplication Transcription (biology) Humans Gene 030304 developmental biology Genetics 0303 health sciences biology Biochemistry Genetics and Molecular Biology(all) DNA Helicases DNA replication Helicase Neurodegenerative Diseases RNA Helicase A 3. Good health biology.protein RNA Polymerase II RNA Helicases 030217 neurology & neurosurgery |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Cell |
| Popis: | El pdf del artículo es el manuscrito de autor.-- et al. Transcription hinders replication fork progression and stability. The ATR checkpoint and specialized DNA helicases assist DNA synthesis across transcription units to protect genome integrity. Combining genomic and genetic approaches together with the analysis of replication intermediates, we searched for factors coordinating replication with transcription. We show that the Sen1/Senataxin DNA/RNA helicase associates with forks, promoting their progression across RNA polymerase II (RNAPII)-transcribed genes. sen1 mutants accumulate aberrant DNA structures and DNA-RNA hybrids while forks clash head-on with RNAPII transcription units. These replication defects correlate with hyperrecombination and checkpoint activation in sen1 mutants. The Sen1 function at the forks is separable from its role in RNA processing. Our data, besides unmasking a key role for Senataxin in coordinating replication with transcription, provide a framework for understanding the pathological mechanisms caused by Senataxin deficiencies and leading to the severe neurodegenerative diseases ataxia with oculomotor apraxia type 2 and amyotrophic lateral sclerosis 4. © 2012 Elsevier Inc. R.B. is supported by the Spanish Ministry of Science and Innovation (RYC-2010-07131 and BFU2011-24909) and the European Community’s FP7 (under grant agreement 293770). This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC) and Telethon-Italy (GGP08057) to G.L. |
| Databáze: | OpenAIRE |
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