Electronic Resource
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 |
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| المؤلفون: | Public Library of Science, 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: | Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden 2015-11-26 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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. |
| مصطلحات الفهرس: | DNA, Neurologie, ddc:570, ddc:610, rvk:XA 10000, rvk:WA 15000, doc-type:article |
| URL: | |
| الاتاحة: | Open access content. Open access content |
| ملاحظة: | application/pdf English |
| Other Numbers: | SUUSL oai:qucosa.de:bsz:14-qucosa-180795 urn:nbn:de:bsz:14-qucosa-180795 PPN474244644 936528403 |
| المصدر المساهم: | STAATS U UNIV From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.ocn936528403 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |