NIH R01 · 2024
Effect of DNA repeat silencing on efficacy of ATRi in prostate cancer treatment
PROJECT SUMMARY Inhibition of the DNA replication checkpoint regulator ATR is a new and promising cancer treatment. ATR inhibitors (ATRi) function as cancer treatments by causing double-stranded breaks (DSBs) at sites of problematic DNA replication. Indeed, we have recently demonstrated that structure-forming repetitive DNA sequences strongly influence on ATRi-driven breakage. However, our recent preliminary studies indicate that abnormal DNA structure formation is not the sole determinant of vulnerability at these sites. We have now shown that ATRi- driven breakage at inverted retroelement repeats is strongly stimulated by treatments that promote their transcription. Moreover, because the…
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