Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors.
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A key modality of non-surgical cancer management is DNA damaging therapy that causes DNA double-strand breaks that are preferentially toxic to rapidly dividing cancer cells. Double-strand break repair capacity is recognized as an important mechanism in drug resistance and is therefore a potential target for adjuvant chemotherapy. Additionally, spontaneous and environmentally induced DSBs are known to promote cancer, making DSB evaluation important as a tool in epidemiology, clinical evaluation and in the development of novel pharmaceuticals. Currently available assays to detect double-strand breaks are limited in throughput and specificity and offer minimal information concerning the kinetics of repair. Here, we present the CometChip, a 96-well platform that enables assessment of double-strand break levels and repair capacity of multiple cell types and conditions in parallel and integrates with standard high-throughput screening and analysis technologies. We demonstrate the ability to detect multiple genetic deficiencies in double-strand break repair and evaluate a set of clinically relevant chemical inhibitors of one of the major double-strand break repair pathways, non-homologous end-joining. While other high-throughput repair assays measure residual damage or indirect markers of damage, the CometChip detects physical double-strand breaks, providing direct measurement of damage induction and repair capacity, which may be useful in developing and implementing treatment strategies with reduced side effects.
SubjectDNA double-strand breaks
neutral comet assay
neutral single-cell electrophoresis assay
DNA Breaks, Double-Stranded
DNA-Activated Protein Kinase
Drug Resistance, Neoplasm
High-Throughput Screening Assays
Published Version (Please cite this version)10.4161/cc.23880
Publication InfoEngelward, BP; Floyd, Scott Richard; Ge, J; Huang, Q; Mutamba, JT; Rowland, EA; ... Yaffe, Michael B (2013). Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors. Cell Cycle, 12(6). pp. 907-915. 10.4161/cc.23880. Retrieved from http://hdl.handle.net/10161/15938.
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Gary Hock and Lyn Proctor Associate Professor of Radiation Oncology
Visiting Research Scholar in the Department of Medicine
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