ArticlePLoS biology2010
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Longitudinal Dynamics of Plasma Neurofilament Light Chain in Hereditary Spastic Paraplegia Type 11 (HSP-SPG11) and Type 15 (HSP-ZFYVE26).Movement disorders : official journal of the Movement Disorder Society · 2026Article
- LXR agonist rescues synaptic dysfunction and degeneration in SPG3A patient-specific iPSC-derived neurons.Acta neuropathologica communications · 2025Article
- Bi-allelic variants in three genes encoding distinct subunits of the vesicular AP-5 complex cause hereditary macular dystrophy.American journal of human genetics · 2025Article
- Article
- Axon demyelination and degeneration in a zebrafishOpen biology · 2024Article
- AP2A2 mutation and defective endocytosis in a Malian family with hereditary spastic paraplegia.Neurobiology of disease · 2024Article
- Maternal regulation of the vertebrate oocyte-to-embryo transition.PLoS genetics · 2024Article
- Mapping the global interactome of the ARF family reveals spatial organization in cellular signaling pathways.Journal of cell science · 2024Article
- Pluripotent Stem Cells as a Preclinical Cellular Model for Studying Hereditary Spastic Paraplegias.International journal of molecular sciences · 2024Review
- Hereditary spastic paraplegia: Novel insights into the pathogenesis and management.SAGE open medicine · 2024Review
- Spatacsin regulates directionality of lysosome trafficking by promoting the degradation of its partner AP5Z1.PLoS biology · 2023Article
- A multi-scale map of protein assemblies in the DNA damage response.Cell systems · 2023Article
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria.Nature communications · 2023Article
- Rescue of lysosomal function as therapeutic strategy for SPG15 hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Hereditary spastic paraplegia (SPG 48) with deafness and azoospermia: A case report.Frontiers in neurology · 2023Article
- Inhibiting mitochondrial fission rescues degeneration in hereditary spastic paraplegia neurons.Brain : a journal of neurology · 2022Article
- The role of autophagy-lysosomal pathway in motor neuron diseases.Biochemical Society transactions · 2022Review
- Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.Bioengineered · 2021Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
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.
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