{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:07:19Z","timestamp":1792030039443,"version":"4.4.0"},"posted":{"date-parts":[[2026,5,1]]},"group-title":"Molecular Biology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R35GM147710"],"award-info":[{"award-number":["R35GM147710"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32GM142619"],"award-info":[{"award-number":["T32GM142619"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"crossref","award":["NXTGN-25-013"],"award-info":[{"award-number":["NXTGN-25-013"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"crossref"}]},{"award":["S10OD034224"],"award-info":[{"award-number":["S10OD034224"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Ataxia-telangiectasia and Rad3-related (ATR) is an essential DNA damage response kinase that protects genome integrity by controlling cell cycle checkpoints, regulating origin firing, stabilizing replication forks, and signaling DNA repair. Due to hyper-proliferation, cancer cells depend on ATR for survival, implicating ATR inhibitors as promising therapeutics. However, variable tumor responses to ATR inhibitors highlights the need to uncover the determinants of cell fate. Here, we show breast cancer sensitivity to ATR inhibition correlates with the appearance of pan-nuclear DNA damage. The fate of these cells is driven by a p53-p21-RB1 axis that triggers a G2-to-G0-like cell cycle exit and is buffered by the p53 inhibitor MDM2. MDM2 inhibition lowers the DNA damage threshold for cell cycle exit and robustly targets ATR inhibitor-resistant cells. Our work reveals cell cycle plasticity as a mechanism determining cell fate during ATR inhibition and identifies MDM2 as a target for increasing ATR inhibitor efficacy.<\/jats:p>","DOI":"10.64898\/2026.04.28.721427","type":"posted-content","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:55:12Z","timestamp":1777661712000},"source":"Crossref","is-referenced-by-count":1,"title":["G2-to-G0 cell cycle exit underlies sensitivity to ATR inhibition via the p53-p21-RB1 axis"],"prefix":"10.64898","author":[{"given":"Celina","family":"Sanchez","sequence":"first","affiliation":[{"name":"Program in Biomedical Sciences, School of Medicine, Oregon Health & Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Origel","family":"Marmolejo","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA"},{"name":"Recursion, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Saldivar","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA"},{"name":"Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050517351051000_2026.04.28.721427v1.1","unstructured":"Morgan, D. 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