A mitotic stopwatch determines cell fate

• 成果类型: Editorial Material
• 署名作者: Bertolin, Agustina P.; Gottifredi, Vanesa
• 署名单位: Francis Crick Institute; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Leloir Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10414
• DOI: 10.1126/science.ado5703
• 发表日期: 2024-03-29
• 页码: 1414-1415
• 关键词: centrosome loss

摘要

Surveillance of mitotic timing prevents amplification of damaged cells Mitosis is a challenging time for cells owing to the potential for structural and numerical chromosomal abnormalities, termed chromosomal instability, which is a hallmark of cancer (1). In M phase, chromosomal instability is prevented by the spindle assembly checkpoint, which delays cell cycle progression until chromosomes are properly attached to spindle microtubules, ensuring proper separation into daughter cells (2). Recently, another M phase checkpoint was described: If a threshold mitotic duration is surpassed, proliferation of daughter cells is arrested in a manner that requires the tumor suppressor p53, the cell cycle inhibitor p21, ubiquitin-specific protease 28 (USP28), and p53-binding protein 1 (53BP1) (3-6). On page 1441 of this issue, Meitinger et al. (7) clarify how this process works, with extended mitosis leading to the assembly of a USP28-53BP1-p53 complex-the mitotic stopwatch-which mediates daughter cell arrest and may prevent cancer development.