Journal
CELL CYCLE
Volume 12, Issue 6, Pages 907-915Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.23880
Keywords
high throughput; neutral single-cell electrophoresis assay; neutral comet assay; microarray; DNA double-strand breaks; DNA repair; non-homologous end-joining; DNA-PK inhibitors
Categories
Funding
- NIEHS Training Grant in Environmental Toxicology [T32-ES007020]
- [U01-ES016045]
- [R21-ES019498]
- [ES015339]
- [CA112967]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available