Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors

David M. Weingeist, Jing Ge, David K. Wood, James T. Mutamba, Qiuying Huang, Elizabeth A. Rowland, Michael B. Yaffe, Scott Floyd, Bevin P. Engelward

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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 doublestrand 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.

Original languageEnglish (US)
Pages (from-to)907-915
Number of pages9
JournalCell Cycle
Issue number6
StatePublished - Mar 15 2013


  • DNA double-strand breaks
  • DNA repair
  • DNA-PK inhibitors
  • High throughput
  • Microarray
  • Neutral comet assay
  • Neutral single-cell electrophoresis assay
  • Non-homologous end-joining


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