biostudies-literatureHuang XNCI NIH HHSNIGMS NIH HHS1065-70https://www.ebi.ac.uk/biostudies/studies/S-EPMC545827biostudies-literatureUnknown102(4)Mitotic catastrophe is the response of mammalian cells to mitotic DNA damage. It produces tetraploid cells with a range of different nuclear morphologies from binucleated to multimicronucleated. In response to DNA damage, checkpoints are activated to delay cell cycle progression and to coordinate repair. Cells in different cell cycle phases use different mechanisms to arrest their cell cycle progression. It has remained unclear whether the termination of mitosis in a mitotic catastrophe is regulated by DNA damage checkpoints. Here, we report the presence of a mitotic exit DNA damage checkpoint in mammalian cells. This checkpoint delays mitotic exit and prevents cytokinesis and, thereby, is responsible for mitotic catastrophe. The DNA damage-induced mitotic exit delay correlates with the inProceedings of the National Academy of Sciences of the United States of AmericaDNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint.PMC545827R01 CA116097R25 GM069234R01 CA116097-01A1Hatcher RTran THuang XZhang LZhang PfalseDNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint.Mitotic catastrophe is the response of mammalian cells to mitotic DNA damage. It produces tetraploid cells with a range of different nuclear morphologies from binucleated to multimicronucleated. In response to DNA damage, checkpoints are activated to delay cell cycle progression and to coordinate repair. Cells in different cell cycle phases use different mechanisms to arrest their cell cycle progression. It has remained unclear whether the termination of mitosis in a mitotic catastrophe is regulated by DNA damage checkpoints. Here, we report the presence of a mitotic exit DNA damage checkpoint in mammalian cells. This checkpoint delays mitotic exit and prevents cytokinesis and, thereby, is responsible for mitotic catastrophe. The DNA damage-induced mitotic exit delay correlates with the in2005-01-01T00:00:00Z2005 Jan2025-04-20T01:38:35.125Z2019-03-27T01:08:32ZS-EPMC5458271565004710.1073/pnas.0409130102