Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors.
Abstract
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.
Type
Journal articleSubject
DNA double-strand breaksDNA repair
DNA-PK inhibitors
high throughput
microarray
neutral comet assay
neutral single-cell electrophoresis assay
non-homologous end-joining
Animals
CHO Cells
Cell Line
Chromones
Cricetinae
DNA Breaks, Double-Stranded
DNA Damage
DNA Repair
DNA-Activated Protein Kinase
Drug Resistance, Neoplasm
Enzyme Inhibitors
High-Throughput Screening Assays
Humans
Morpholines
Neoplasms
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https://hdl.handle.net/10161/15938Published Version (Please cite this version)
10.4161/cc.23880Publication Info
Weingeist, David M; Ge, Jing; Wood, David K; Mutamba, James T; Huang, Qiuying; Rowland,
Elizabeth A; ... Engelward, Bevin P (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 https://hdl.handle.net/10161/15938.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Scott Richard Floyd
Gary Hock and Lyn Proctor Associate Professor of Radiation Oncology

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