Localizing Site-Specific DNA Damage
How it Works
Many new targeted cancer drugs function by inhibiting specific DNA Damage Response (DDR) pathways or by altering DNA directly. This increases the level of DNA damage and chromosomal breaks selectively in cancer cells that are most often already defined by DNA repair deficiencies.
These DNA breaks can occur randomly throughout the genome, or at specific vulnerable sites. By identifying where along the cell’s chromosomes DNA breaks occur from exposure to different DNA-damaging drugs, we can discover novel genomic sequences that may predict a strong therapeutic response.
What we'll do for you
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>50% of breaks in MDA-MB-231 cells treated with a pre-clinical targeted cancer drug, ATRi, occur at unique AT-rich repetitive sequences that form hairpin structures
From “Genome-wide identification of structure-forming repeats as principal sites of fork collapse upon ATR inhibition” (Molecular Cell, 2018)
BreakSight works with academic research labs and pharma companies to identify genomic sequences that are vulnerable to breakage upon treatment of cells with compound(s) of interest. In doing so, BreakSight can uncover previously unknown effects on the genome and highlight a broader range of DNA sequences that may predict therapeutic efficacy of the compound(s). This is accomplished by a technique that labels and retrieves DNA breaks from the genome of actively replicating cells exposed to the compound(s).
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Performance of next-generation sequencing (NGS) on the retrieved DNA break fragments reveals the chromosomal locations and DNA sequences associated with breakage, detected by significant sequence read build-ups at regions across the genome (shown on left).
How the findings can lead to biomarker identification
Discover the DNA sequences that break most frequently upon [Your Drug] treatment
Identify the presence or absence of these sequences in individual cancer genomes to correlate drug response