DNA repair is essential for cellular homeostasis and is a key mediator of cancer cell survival following genotoxic therapies. Because tumor evolution often remodels DNA repair capacity to counteract these therapies, there is significant interest in “precision medicine” approaches to determine whether a tumor will be responsive to a therapy prior to its delivery and to track the development of tumor resistance during therapy.
Single-cell analysis of DNA repair capacity
We are developing a sequencing-based assay for measuring DNA repair capacity that can be scaled to measure repair events catalyzed by endogenous activities in primary cells on substrates containing any synthetically accessible DNA modification.
We previously developed Excision-seq to study the genome-wide distribution of modified nucleobases in DNA. We have used Excision-seq to study the distribution of uracil and pyrimidine dimers in genomic DNA that accumulate under specific conditions. A related method called XR-seq has been developed in Aziz Sancar’s lab to study the distribution of pyrimidine dimers in genomic DNA.
This work has been funded by:
- Denver chapter of the Golfers Against Cancer.
- A Research Scholar Grant from the American Cancer Society (RSG-13-216-01-DMC)
- A Basil O’Connor Starter Scholar Research Award from the March of Dimes