Academic Journal
A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia
| العنوان: | A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia |
|---|---|
| المؤلفون: | Buchholz, Frank, Słabicki, Mikołaj, Theis, Mirko, Krastev, Dragomir B., Samsonov, Sergey, Mundwiller, Emeline, Junqueira, Magno, Paszkowski-Rogacz, Maciej, Teyra, Joan, Heninger, Anne-Kristin, Poser, Ina, Prieur, Fabienne, Truchetto, Jérémy, Confavreux, Christian, Marelli, Cécilia, Durr, Alexandra, Camdessanche, Jean Philippe, Brice, Alexis, Shevchenko, Andrej, Pisabarro, M. Teresa, Stevanin, Giovanni |
| المصدر: | Plos biology, Bd. 8 (2010) Nr. 6; ISSN 1544-9173 |
| بيانات النشر: | Public Library of Science, 2010. |
| سنة النشر: | 2010 |
| المجموعة: | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Original Material: | urn:nbn:de:bsz:14-qucosa-180795 474244644 |
| مصطلحات موضوعية: | DNA, Neurologie, DNA, info:eu-repo/classification/ddc/570, ddc:570, info:eu-repo/classification/ddc/610, ddc:610 |
| الوصف: | DNA repair is essential to maintain genome integrity, and genes with roles in DNA repair are frequently mutated in a variety of human diseases. Repair via homologous recombination typically restores the original DNA sequence without introducing mutations, and a number of genes that are required for homologous recombination DNA double-strand break repair (HR-DSBR) have been identified. However, a systematic analysis of this important DNA repair pathway in mammalian cells has not been reported. Here, we describe a genome-scale endoribonuclease-prepared short interfering RNA (esiRNA) screen for genes involved in DNA double strand break repair. We report 61 genes that influenced the frequency of HR-DSBR and characterize in detail one of the genes that decreased the frequency of HR-DSBR. We show that the gene KIAA0415 encodes a putative helicase that interacts with SPG11 and SPG15, two proteins mutated in hereditary spastic paraplegia (HSP). We identify mutations in HSP patients, discovering KIAA0415/SPG48 as a novel HSP-associated gene, and show that a KIAA0415/SPG48 mutant cell line is more sensitive to DNA damaging drugs. We present the first genome-scale survey of HR-DSBR in mammalian cells providing a dataset that should accelerate the discovery of novel genes with roles in DNA repair and associated medical conditions. The discovery that proteins forming a novel protein complex are required for efficient HR-DSBR and are mutated in patients suffering from HSP suggests a link between HSP and DNA repair. |
| Original Identifier: | oai:qucosa:de:qucosa:28927 |
| نوع الوثيقة: | Article |
| اللغة: | English |
| DOI: | 10.1371/journal.pbio.1000408 |
| الاتاحة: | https://tud.qucosa.de/id/qucosa%3A28927 https://tud.qucosa.de/api/qucosa%3A28927/attachment/ATT-0/ |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsndl.DRESDEN.oai.qucosa.de.qucosa.28927 |
| قاعدة البيانات: | Networked Digital Library of Theses & Dissertations |
| DOI: | 10.1371/journal.pbio.1000408 |
|---|