Preprint Highlight: ATR protects centromere identity by promoting DAXX association with PML nuclear bodies.

ATR ( Ataxia telangiectasia and Rad3-related) is an essential kinase in the DNA damage response, but it also displays some DNA damage-independent roles in mitosis. By using an ATR inhibitor and genetic manipulations, this work shows that ATR phosphorylates the histone H3.3 chaperone DAXX to maintain its localization to PML (promyelocytic leukemia) nuclear bodies in interphase cells and thus ensures proper localization of centromere protein A (CENP-A) to centromeres. Reduced CENP-A localization on centromeres after ATR inhibition lasted through mitosis, resulting in chromosome segregation errors. This work adds to the understanding of ATR's role in genome stability independent of DNA damage response and may shed new light on how to reduce toxicity of ATR inhibitor-based cancer therapeutics. This preprint has been assigned the following badge: New Hypothesis. Read the preprint on bioRxiv ( Trier et al., 2022 ): https://doi.org/10.1101/2022.09.26.509554 .