[PDF][PDF] Thymidine rescues ATR kinase inhibitor-induced deoxyuridine contamination in genomic DNA, cell death, and interferon-α/β expression
N Sugitani, FP Vendetti, AJ Cipriano, P Pandya… - Cell reports, 2022 - cell.com
ATR kinase is a central regulator of the DNA damage response (DDR) and cell cycle
checkpoints. ATR kinase inhibitors (ATRi's) combine with radiation to generate CD8+ T cell-
dependent responses in mouse models of cancer. We show that ATRi's induce cyclin-
dependent kinase 1 (CDK1)-dependent origin firing across active replicons in CD8+ T cells
activated ex vivo while simultaneously decreasing the activity of rate-limiting enzymes for
nucleotide biosynthesis. These pleiotropic effects of ATRi induce deoxyuridine (dU) …
checkpoints. ATR kinase inhibitors (ATRi's) combine with radiation to generate CD8+ T cell-
dependent responses in mouse models of cancer. We show that ATRi's induce cyclin-
dependent kinase 1 (CDK1)-dependent origin firing across active replicons in CD8+ T cells
activated ex vivo while simultaneously decreasing the activity of rate-limiting enzymes for
nucleotide biosynthesis. These pleiotropic effects of ATRi induce deoxyuridine (dU) …
Thymidine rescues ATR kinase inhibition induced deoxyuridine contamination in genomic DNA, cell death, and Type 1 interferon expression
N Sugitani, FP Vendetti, AJ Cipriano, P Pandya… - bioRxiv, 2022 - biorxiv.org
SUMMARY ATR kinase is a central regulator of the DNA damage response (DDR) and cell
cycle checkpoints. ATR kinase inhibitors (ATRi's) combine with radiation to generate CD8+ T
cell-dependent responses in mouse models of cancer. We show that ATRi's induce CDK1-
dependent origin firing across active replicons in CD8+ T cells activated ex vivo while
simultaneously decreasing the activity of rate-limiting enzymes for nucleotide biosynthesis.
These pleiotropic effects of ATRi induce deoxyuridine (dU) contamination in genomic DNA …
cycle checkpoints. ATR kinase inhibitors (ATRi's) combine with radiation to generate CD8+ T
cell-dependent responses in mouse models of cancer. We show that ATRi's induce CDK1-
dependent origin firing across active replicons in CD8+ T cells activated ex vivo while
simultaneously decreasing the activity of rate-limiting enzymes for nucleotide biosynthesis.
These pleiotropic effects of ATRi induce deoxyuridine (dU) contamination in genomic DNA …