A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia

• DOI: 10.1371/journal.pbio.1000408
• Publication Date: 2010-06-29T19:49:58Z
• Authors: Mikołaj Słabicki; Mirko Theis; Dragomir B. Krastev; Sergey Samsonov; Emeline Mundwiller; Magno Junqueira; Maciej Paszkowski...; Joan Teyra; Anne-Kristin Heni...; Ina Poser; Fabienne Prieur; Jérémy Truchetto; Christian Confavreux; Cécilia Marelli; Alexandra Durr; Jean Philippe Cam...; Alexis Brice; Andrej Shevchenko; M. Teresa Pisabarro; Giovanni Stevanin; Frank Buchholz
• Keywords: Hereditary Spastic Paraplegia; Non-homologous end joining

DNA repair is essential to maintain genome integrity, and genes with roles in are frequently mutated a variety of human diseases. Repair via homologous recombination typically restores the original sequence without introducing mutations, number that required for double-strand break (HR-DSBR) have been identified. However, systematic analysis this important pathway mammalian cells has not reported. Here, we describe genome-scale endoribonuclease-prepared short interfering RNA (esiRNA) screen involved double strand repair. We report 61 influenced frequency HR-DSBR characterize detail one decreased HR-DSBR. show gene KIAA0415 encodes putative helicase interacts SPG11 SPG15, two proteins hereditary spastic paraplegia (HSP). identify mutations HSP patients, discovering KIAA0415/SPG48 as novel HSP-associated gene, mutant cell line more sensitive damaging drugs. present first survey providing dataset should accelerate discovery associated medical conditions. The forming protein complex efficient patients suffering from suggests link between