{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:09:48Z","timestamp":1790737788774,"version":"4.1.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MRC New Investigator Research Grant","award":["MR\/X019098\/1"],"award-info":[{"award-number":["MR\/X019098\/1"]}]},{"name":"Academy of Medical Science","award":["SBF008\\1109"],"award-info":[{"award-number":["SBF008\\1109"]}]},{"name":"Barts Charity Seed","award":["G-003048"],"award-info":[{"award-number":["G-003048"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The use of PARP inhibitors (PARPi) has profoundly changed the treatment of BRCA1\/BRCA2-mutated cancers. Despite this, acquired resistance to PARPi has become a major challenge in the clinic. Hence, a more detailed understanding of the mechanisms underlying PARPi sensitivity is crucially needed. Here, we show that loss of the alternative clamp loader complex CHTF18\u2013RFC2\/5 leads to a remarkable sensitization to PARPi. Loss of CHTF18 is not associated with defective RAD51 foci formation excluding a defect in homologous recombination. On the contrary, treatment with PARPi triggers replicative gap accumulation in CHTF18 knockout (KO) cells. By performing transient silencing experiments, we highlight PARP1\u2013PARP2 trapping at replicative gaps as a major determinant of sensitivity to these compounds. Crucially, loss of 53BP1 does not rescue PARPi sensitivity in CHTF18 KO cells, outlining Pol\u03b5 and the CHTF18\u2013RFC2\/5 complex as potential novel targets for cancer therapeutics.<\/jats:p>","DOI":"10.1093\/narcan\/zcag013","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:14:10Z","timestamp":1779794050000},"source":"Crossref","is-referenced-by-count":1,"title":["Loss of CHTF18\u2013RFC2\/5 leads to replicative gaps and sensitivity to PARP inhibitors"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-8632","authenticated-orcid":false,"given":"Lauryn","family":"Buckley-Benbow","sequence":"first","affiliation":[{"name":"Centre for Cancer Cell & Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square EC1M 6BQ , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-0257","authenticated-orcid":false,"given":"Meryem","family":"Ozgencil","sequence":"additional","affiliation":[{"name":"Centre for Cancer Cell & Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square EC1M 6BQ , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5677-7589","authenticated-orcid":false,"given":"Alessia","family":"Tardocchi","sequence":"additional","affiliation":[{"name":"Centre for Cancer Cell & Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square EC1M 6BQ , London ,","place":["United Kingdom"]},{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 Federico II , 80131 Napoli ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-3836","authenticated-orcid":false,"given":"Alessandro","family":"Agnarelli","sequence":"additional","affiliation":[{"name":"Centre for Cancer Cell & Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square EC1M 6BQ , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2062-7113","authenticated-orcid":false,"given":"Roberto","family":"Bellelli","sequence":"additional","affiliation":[{"name":"Centre for Cancer Cell & Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square EC1M 6BQ , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"2026060305283218400_B1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev-pathol-012414-040424","article-title":"DNA replication stress as a hallmark of cancer","volume":"10","author":"Macheret","year":"2015","journal-title":"Annu Rev Pathol"},{"key":"2026060305283218400_B2","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1101\/gad.349431.122","article-title":"DNA repair defects in cancer and therapeutic opportunities","volume":"36","author":"Hopkins","year":"2022","journal-title":"Genes Dev"},{"key":"2026060305283218400_B3","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1126\/science.aam7344","article-title":"PARP inhibitors: synthetic lethality in the 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