{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:09:46Z","timestamp":1790737786536,"version":"4.1.0"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["MSCA-IF-2017-794054"],"award-info":[{"award-number":["MSCA-IF-2017-794054"]}]},{"name":"Andalusian Regional Government-Junta de Andaluc\u00eda","award":["EMC21_00057"],"award-info":[{"award-number":["EMC21_00057"]}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["PID2019-104195G"],"award-info":[{"award-number":["PID2019-104195G"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009042","name":"Universidad de Sevilla","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>DNA replication faces challenges from DNA lesions originated from endogenous or exogenous sources of stress, leading to the accumulation of single-stranded DNA (ssDNA) that triggers the activation of the ATR checkpoint response. To complete genome replication in the presence of damaged DNA, cells employ DNA damage tolerance mechanisms that operate not only at stalled replication forks but also at ssDNA gaps originated by repriming of DNA synthesis downstream of lesions. Here, we demonstrate that human cells accumulate post-replicative ssDNA gaps following replicative stress induction. These gaps, initiated by PrimPol repriming and expanded by the long-range resection factors EXO1 and DNA2, constitute the principal origin of the ssDNA signal responsible for ATR activation upon replication stress, in contrast to stalled forks. Strikingly, the loss of EXO1 or DNA2 results in synthetic lethality when combined with BRCA1 deficiency, but not BRCA2. This phenomenon aligns with the observation that BRCA1 alone contributes to the expansion of ssDNA gaps. Remarkably, BRCA1-deficient cells become addicted to the overexpression of EXO1,\u00a0DNA2 or BLM. This dependence on long-range resection unveils a new vulnerability of BRCA1-mutant tumors, shedding light on potential therapeutic targets for these cancers.<\/jats:p>","DOI":"10.1093\/nar\/gkae317","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T12:39:21Z","timestamp":1712925561000},"page":"6376-6391","source":"Crossref","is-referenced-by-count":29,"title":["EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-1604","authenticated-orcid":false,"given":"N\u00e9stor","family":"Garc\u00eda-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-CSIC-Universidad Pablo de Olavide , Sevilla , Spain"},{"name":"Departamento de Gen\u00e9tica, Universidad de Sevilla , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iria","family":"Dom\u00ednguez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-CSIC-Universidad Pablo de Olavide , Sevilla , Spain"},{"name":"Departamento de Gen\u00e9tica, Universidad de Sevilla , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del\u00a0Carmen","family":"Dom\u00ednguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-CSIC-Universidad Pablo de Olavide , Sevilla , Spain"},{"name":"Departamento de Gen\u00e9tica, Universidad de Sevilla , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1756-4449","authenticated-orcid":false,"given":"Pablo","family":"Huertas","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-CSIC-Universidad Pablo de Olavide , Sevilla , Spain"},{"name":"Departamento de Gen\u00e9tica, Universidad de Sevilla , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"2024062400042936900_B1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ncb2897","article-title":"Causes and consequences of replication stress","volume":"16","author":"Zeman","year":"2014","journal-title":"Nat. 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