The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response
Open accessAbstract
Repair of DNA double-strand breaks is critical to genomic stability and the prevention of developmental disorders and cancer. A central pathway for this repair is homologous recombination (HR). Most knowledge of HR is derived from work in prokaryotic and eukaryotic model organisms. We carried out a genome-wide siRNA-based screen in human cells. Among positive regulators of HR we identified networks of DNA-damage-response and pre-mRNA-processing proteins, and among negative regulators we identified a phosphatase network. Three candidate proteins localized to DNA lesions, including RBMX, a heterogeneous nuclear ribonucleoprotein that has a role in alternative splicing. RBMX accumulated at DNA lesions through multiple domains in a poly(ADP-ribose) polymerase 1-dependent manner and promoted HR by facilitating proper BRCA2 expression. Our screen also revealed that off-target depletion of RAD51 is a common source of RNAi false positives, raising a cautionary note for siRNA screens and RNAi-based studies of HR.
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“CRISPRi represents an important advance over RNAi, since it lacks the pervasive off-target effects (Gilbert et al., 2014) inherent to RNAi-based screening approaches (Adamson et al., 2012; Jackson et al., 2003; Kaelin, 2012).”
From CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons (2019) · cites this paper as Adamson et al., 2012
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Metadata
- Authors
- Adamson, B., Smogorzewska, A., Sigoillot, F. D., King, R. W., & Elledge, S. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Elledge, Stephen J.
- Venue
- Nature Cell Biology
- Published
- 2012-02-19
- Volume
- 14
- Issue
- 3
- Pages
- 318-328
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC3290715
- OpenAlex
- W2052973047
- Cited by
- 433
- References
- 36
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 25 · 2023: 34 · 2022: 28 · 2021: 43 · 2020: 40 · 2019: 33 · 2018: 30 · 2017: 30 · 2016: 30 · 2015: 33 · 2014: 34 · 2013: 35 · 2012: 8
- FWCI
- 14.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (T32CA09216, T32CA009216)
- National Institute of General Medical Sciences (R37GM044664, R01GM044664)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- homologous recombination, RBMX, DNA damage response, DNA double-strand break repair, siRNA screen, off-target effects, RAD51, PARP1, BRCA2, pre-mRNA processing, RNA-binding proteins, alternative splicing, heterogeneous nuclear ribonucleoproteins
- MeSH terms
- DNA Damage, DNA Repair, Humans, Microscopy, Fluorescence, Models, Genetic, Nuclear Proteins, Poly(ADP-ribose) Polymerases, RNA Precursors, Transcription Factors, Immunoblotting, Genome, Human, RNA-Binding Proteins, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, BRCA2 Protein, Nuclear Pore Complex Proteins, Heterogeneous-Nuclear Ribonucleoproteins, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Green Fluorescent Proteins, Rad51 Recombinase, Gene Regulatory Networks, Histone Chaperones, Homologous Recombination
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