{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:38:06Z","timestamp":1788514686097,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Foundation for Cancer Research (Fondazione AIRC)","award":["IG2018#22233"],"award-info":[{"award-number":["IG2018#22233"]}]},{"name":"Italian Foundation for Cancer Research (Fondazione AIRC)","award":["Ex 60%"],"award-info":[{"award-number":["Ex 60%"]}]},{"name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca (MIUR)","award":["IG2018#22233"],"award-info":[{"award-number":["IG2018#22233"]}]},{"name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca (MIUR)","award":["Ex 60%"],"award-info":[{"award-number":["Ex 60%"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed in a subgroup of T-cell acute lymphoblastic (T-ALL) samples, especially those with NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how BCAT1 regulates this sensitivity remains uncertain. Here, we provide further clues on its chemo-sensitizing effect. Indeed, BCAT1 protein regulates the non-homologous end joining (c-NHEJ) DNA repair pathway by physically associating with the KU70\/KU80 heterodimer. BCAT1 inhibition during active repair of DNA double-strand breaks (DSBs) led to increased KU70\/KU80 acetylation and impaired c-NHEJ repair, a dramatic increase in DSBs, and ultimately cell death. Our results suggest that, in T-ALL, BCAT1 possesses non-metabolic functions that confer a drug resistance mechanism and that targeting BCAT1 activity presents a novel strategy to improve chemotherapy response in T-ALL patients.<\/jats:p>","DOI":"10.3390\/ijms252413571","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T11:17:22Z","timestamp":1734520642000},"page":"13571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["BCAT1 Associates with DNA Repair Proteins KU70 and KU80 and Contributes to Regulate DNA Repair in T-Cell Acute Lymphoblastic Leukemia (T-ALL)"],"prefix":"10.3390","volume":"25","author":[{"given":"Valeria","family":"Tosello","sequence":"first","affiliation":[{"name":"Basic and Translational Oncology Unit, Veneto Institute of Oncology IOV\u2014IRCCS, 35127 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3907-2186","authenticated-orcid":false,"given":"Chiara","family":"Rompietti","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV\u2014IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adonia E.","family":"Papathanassiu","sequence":"additional","affiliation":[{"name":"Ergon Pharmaceuticals, LLC., Washington, DC 20011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-2733","authenticated-orcid":false,"given":"Giorgio","family":"Arrigoni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35122 Padua, Italy"},{"name":"Proteomics Center, University of Padua and Azienda Ospedaliera of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4241-563X","authenticated-orcid":false,"given":"Erich","family":"Piovan","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV\u2014IRCCS, 35128 Padua, Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: A comprehensive review and 2017 update","volume":"7","author":"Terwilliger","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/S0140-6736(08)60457-2","article-title":"Acute lymphoblastic leukaemia","volume":"371","author":"Pui","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nrc.2016.63","article-title":"The genetics and mechanisms of T cell acute lymphoblastic leukaemia","volume":"16","author":"Belver","year":"2016","journal-title":"Nat. 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