Characterization of ATR Kinase Function in Quiescent Keratinocytes Exposed to Solar Simulating UV Radiation

This study investigates the role of ATR kinase in quiescent human keratinocytes exposed to solar-simulated UV radiation (SSL). The ATR inhibitor VE-822 did not affect cell viability without UV exposure, indicating ATR is not essential for survival without genotoxic stress. However, after SSL exposure, ATR inhibition reduced long-term cell proliferation and impaired DNA damage signaling, as shown by decreased phosphorylation of ATR targets KAP1 and CHK2, and reduced γH2AX levels. VE-822 treatment delayed and reduced activation of DNA repair proteins, and increased PCNA retention on chromatin suggested issues with DNA repair complex resolution. These results highlight ATR's critical role in DNA repair and cell survival under UV stress, and VE-822's effectiveness as an ATR inhibitor, offering insights for developing strategies to protect skin cells from UV damage.