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Here, we demonstrate that cyclin B3, an evolutionarily divergent B-type cyclin previously thought to function exclusively in female meiosis, is expressed in mitotic cells and interacts with both CDK1 and CDK2. We show that cyclin B3-CDK1\/2 is essential for timely mitotic progression by ensuring proper chromosome alignment and stable kinetochore-microtubule interactions, while its overexpression accelerates mitosis and improves chromosome alignment kinetics. Through phospho-mass spectrometry, we identify several kinetochore and mitotic spindle components as substrates of cyclin B3-CDK1\/2 in mitosis. Notably, cyclin B3 depletion disrupts mitotic progression in most cancer cell lines tested \u2013 including colorectal, osteosarcoma, and breast cancer models \u2013 while non-transformed cells are largely unaffected. These findings identify cyclin B3-CDK1\/2 as a novel driver of mitotic progression and reveal a preferential dependency in a subset of cancer cells that may represent a potential therapeutic vulnerability.<\/jats:p>","DOI":"10.64898\/2026.09.28.754947","type":"posted-content","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:30:16Z","timestamp":1790659816000},"source":"Crossref","is-referenced-by-count":0,"title":["A Meiotic B-type Cyclin Selectively Drives Mitotic Progression and Fidelity in Cancer Cells"],"prefix":"10.64898","author":[{"given":"Amrutha","family":"Kizhedathu","sequence":"first","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Cao Ngoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clinton","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Moghareh","sequence":"additional","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vy","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"},{"name":"Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, 85308, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Powel","family":"Mousaian","sequence":"additional","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Vertiz","sequence":"additional","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-3186","authenticated-orcid":false,"given":"Claudia A.","family":"Benavente","sequence":"additional","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"},{"name":"Department of Pharmaceutical Sciences, University of California Irvine, Irvine CA 92697, USA"},{"name":"Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-9006","authenticated-orcid":false,"given":"Pablo","family":"Lara-Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Developmental & Cell Biology, University of California Irvine, Irvine CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100111102278000_2026.09.28.754947v1.1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000926"},{"key":"2026100111102278000_2026.09.28.754947v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.09.005"},{"key":"2026100111102278000_2026.09.28.754947v1.3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41572-022-00393-3","article-title":"Small round cell sarcomas","volume":"8","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"2026100111102278000_2026.09.28.754947v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13635"},{"key":"2026100111102278000_2026.09.28.754947v1.5","doi-asserted-by":"crossref","unstructured":"Crncec, A. , H.W. 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