{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:01:09Z","timestamp":1768507269430,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,7]]},"group-title":"Molecular Biology","reference-count":70,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>The ATM protein kinase is a master regulator of the DNA damage response and also an important sensor of oxidative stress. Analysis of gene expression in Ataxia-telangiectasia patient brain tissue shows that large-scale transcriptional changes occur in patient cerebellum that correlate with expression level and GC content of transcribed genes. In human neuron-like cells in culture we map locations of poly-ADP-ribose and RNA-DNA hybrid accumulation genome-wide with ATM inhibition and find that these marks also coincide with high transcription levels, active transcription histone marks, and high GC content. Antioxidant treatment reverses the accumulation of R-loops in transcribed regions, consistent with the central role of ROS in promoting these lesions. Based on these results we postulate that transcription-associated lesions accumulate in ATM-deficient cells and that the single-strand breaks and PARylation at these sites ultimately generate changes in transcription that compromise cerebellum function and lead to neurodegeneration over time in A-T patients.<\/jats:p>","DOI":"10.1101\/2023.12.06.570417","type":"posted-content","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T23:20:15Z","timestamp":1701991215000},"source":"Crossref","is-referenced-by-count":0,"title":["Regulation of transcription patterns, poly-ADP-ribose, and RNA-DNA hybrids by the ATM protein kinase"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4473-9424","authenticated-orcid":false,"given":"Phillip 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