A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia.
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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2010
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/f5f2a05ab4b94ace913261bc60a1e2dd |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:f5f2a05ab4b94ace913261bc60a1e2dd |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:f5f2a05ab4b94ace913261bc60a1e2dd2021-12-02T19:54:47ZA genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia.1544-91731545-788510.1371/journal.pbio.1000408https://doaj.org/article/f5f2a05ab4b94ace913261bc60a1e2dd2010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20613862/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885DNA 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.Mikołaj SłabickiMirko TheisDragomir B KrastevSergey SamsonovEmeline MundwillerMagno JunqueiraMaciej Paszkowski-RogaczJoan TeyraAnne-Kristin HeningerIna PoserFabienne PrieurJérémy TruchettoChristian ConfavreuxCécilia MarelliAlexandra DurrJean Philippe CamdessancheAlexis BriceAndrej ShevchenkoM Teresa PisabarroGiovanni StevaninFrank BuchholzPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 8, Iss 6, p e1000408 (2010) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Biology (General) QH301-705.5 |
| spellingShingle |
Biology (General) QH301-705.5 Mikołaj Słabicki Mirko Theis Dragomir B Krastev Sergey Samsonov Emeline Mundwiller Magno Junqueira Maciej Paszkowski-Rogacz Joan Teyra Anne-Kristin Heninger Ina Poser Fabienne Prieur Jérémy Truchetto Christian Confavreux Cécilia Marelli Alexandra Durr Jean Philippe Camdessanche Alexis Brice Andrej Shevchenko M Teresa Pisabarro Giovanni Stevanin Frank Buchholz A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. |
| description |
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. |
| format |
article |
| author |
Mikołaj Słabicki Mirko Theis Dragomir B Krastev Sergey Samsonov Emeline Mundwiller Magno Junqueira Maciej Paszkowski-Rogacz Joan Teyra Anne-Kristin Heninger Ina Poser Fabienne Prieur Jérémy Truchetto Christian Confavreux Cécilia Marelli Alexandra Durr Jean Philippe Camdessanche Alexis Brice Andrej Shevchenko M Teresa Pisabarro Giovanni Stevanin Frank Buchholz |
| author_facet |
Mikołaj Słabicki Mirko Theis Dragomir B Krastev Sergey Samsonov Emeline Mundwiller Magno Junqueira Maciej Paszkowski-Rogacz Joan Teyra Anne-Kristin Heninger Ina Poser Fabienne Prieur Jérémy Truchetto Christian Confavreux Cécilia Marelli Alexandra Durr Jean Philippe Camdessanche Alexis Brice Andrej Shevchenko M Teresa Pisabarro Giovanni Stevanin Frank Buchholz |
| author_sort |
Mikołaj Słabicki |
| title |
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. |
| title_short |
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. |
| title_full |
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. |
| title_fullStr |
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. |
| title_full_unstemmed |
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. |
| title_sort |
genome-scale dna repair rnai screen identifies spg48 as a novel gene associated with hereditary spastic paraplegia. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/f5f2a05ab4b94ace913261bc60a1e2dd |
| work_keys_str_mv |
AT mikołajsłabicki agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT mirkotheis agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT dragomirbkrastev agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT sergeysamsonov agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT emelinemundwiller agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT magnojunqueira agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT maciejpaszkowskirogacz agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT joanteyra agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT annekristinheninger agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT inaposer agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT fabienneprieur agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT jeremytruchetto agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT christianconfavreux agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT ceciliamarelli agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT alexandradurr agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT jeanphilippecamdessanche agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT alexisbrice agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT andrejshevchenko agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT mteresapisabarro agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT giovannistevanin agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT frankbuchholz agenomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT mikołajsłabicki genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT mirkotheis genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT dragomirbkrastev genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT sergeysamsonov genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT emelinemundwiller genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT magnojunqueira genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT maciejpaszkowskirogacz genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT joanteyra genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT annekristinheninger genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT inaposer genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT fabienneprieur genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT jeremytruchetto genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT christianconfavreux genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT ceciliamarelli genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT alexandradurr genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT jeanphilippecamdessanche genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT alexisbrice genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT andrejshevchenko genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT mteresapisabarro genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT giovannistevanin genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia AT frankbuchholz genomescalednarepairrnaiscreenidentifiesspg48asanovelgeneassociatedwithhereditaryspasticparaplegia |
| _version_ |
1718375878168150016 |