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A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia
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نویسنده
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słabicki m. ,theis m. ,krastev d.b. ,samsonov s. ,mundwiller e. ,junqueira m. ,paszkowski-rogacz m. ,teyra j. ,heninger a.-k. ,poser i. ,prieur f. ,truchetto j. ,confavreux c. ,marelli c. ,durr a. ,camdessanche j.p. ,brice a. ,shevchenko a. ,teresa pisabarro m. ,stevanin g. ,buchholz f.
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منبع
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plos biology - 2010 - دوره : 8 - شماره : 6
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چکیده
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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. © 2010 słabicki et al.
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آدرس
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max planck institute for molecular cell biology and genetics,dresden, Germany, max planck institute for molecular cell biology and genetics,dresden, Germany, max planck institute for molecular cell biology and genetics,dresden, Germany, structural bioinformatics,biotec tu,dresden, Germany, inserm,unit 975 paris,france,université pierre et marie curie-paris6,centre de recherche de l'institut du cerveau et de la moelle epiniére,paris,france,cnrs,unité mixte de recherche,7225 paris, France, max planck institute for molecular cell biology and genetics,dresden, Germany, max planck institute for molecular cell biology and genetics,dresden, Germany, structural bioinformatics,biotec tu,dresden, Germany, max planck institute for molecular cell biology and genetics,dresden, Germany, max planck institute for molecular cell biology and genetics,dresden, Germany, hôpital nord,saint etienne, France, inserm,unit 975 paris,france,université pierre et marie curie-paris6,centre de recherche de l'institut du cerveau et de la moelle epiniére,paris,france,cnrs,unité mixte de recherche,7225 paris, France, hôpital neurologique,lyon, France, inserm,unit 975 paris,france,université pierre et marie curie-paris6,centre de recherche de l'institut du cerveau et de la moelle epiniére,paris,france,cnrs,unité mixte de recherche,7225 paris,france,aphp,pitié-salpêtriére hospital,department of genetics and cytogenetics,paris, France, inserm,unit 975 paris,france,université pierre et marie curie-paris6,centre de recherche de l'institut du cerveau et de la moelle epiniére,paris,france,cnrs,unité mixte de recherche,7225 paris,france,aphp,pitié-salpêtriére hospital,department of genetics and cytogenetics,paris, France, hôpital nord,saint etienne, France, inserm,unit 975 paris,france,université pierre et marie curie-paris6,centre de recherche de l'institut du cerveau et de la moelle epiniére,paris,france,cnrs,unité mixte de recherche,7225 paris,france,aphp,pitié-salpêtriére hospital,department of genetics and cytogenetics,paris, France, max planck institute for molecular cell biology and genetics,dresden, Germany, structural bioinformatics,biotec tu,dresden, Germany, inserm,unit 975 paris,france,université pierre et marie curie-paris6,centre de recherche de l'institut du cerveau et de la moelle epiniére,paris,france,cnrs,unité mixte de recherche,7225 paris,france,aphp,pitié-salpêtriére hospital,department of genetics and cytogenetics,paris, France, max planck institute for molecular cell biology and genetics,dresden, Germany
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Authors
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