{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:31:41Z","timestamp":1787329901215,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472749"],"award-info":[{"award-number":["82472749"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Loss of chromosome 16q is a recurrent genomic alteration in bladder and prostate cancers and is associated with poor clinical outcomes. However, the mechanisms by which 16q loss contributes to tumor progression remain poorly understood. Here, we identify the deubiquitinase CYLD as a major contributor to genomic instability associated with chromosome 16q deletion. Mechanistically, CYLD stabilizes the 53BP1 regulator TIRR by removing K48\u2010linked polyubiquitin chains, thereby preventing excessive accumulation of 53BP1 at sites of DNA damage and maintaining efficient homologous recombination repair. Loss of CYLD disrupts this regulation, shifting DNA double\u2010strand break repair toward 53BP1\u2010dependent non\u2010homologous end joining, leading to homologous recombination deficiency. Consequently, CYLD\u2010deficient tumor cells exhibit increased sensitivity to PARP inhibitors. Together, these findings establish CYLD as a critical regulator of DNA double\u2010strand break repair pathway choice and suggest that CYLD loss, or chromosome 16q deletion, may serve as a biomarker of genomic instability and a predictor of response to PARP inhibitor therapy.<\/jats:p>","DOI":"10.1002\/advs.77298","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:38:35Z","timestamp":1787326715000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of CYLD on Chromosome 16q Impairs Homologous Recombination and Genomic Stability Through TIRR Degradation"],"prefix":"10.1002","author":[{"given":"Mingming","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an People's Republic of 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