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Journal articles
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia.
Abstract : 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.
Cited literature [63 references]
https://www.hal.inserm.fr/inserm-00707271
Contributor : Delphine Autard <>
Submitted on : Tuesday, June 12, 2012 - 12:18:48 PM
Last modification on : Thursday, December 10, 2020 - 3:42:24 AM
Long-term archiving on: : Thursday, September 13, 2012 - 2:26:18 AM
Contributor : Delphine Autard <>
Submitted on : Tuesday, June 12, 2012 - 12:18:48 PM
Last modification on : Thursday, December 10, 2020 - 3:42:24 AM
Long-term archiving on: : Thursday, September 13, 2012 - 2:26:18 AM
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journal.pbio.1000408.pdf
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