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Content Provider | PubMed Central |
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Author | Wong, Po Yee Tang, Ma Hoi Lee, Hyun-jung Poon, Randy Y. C. |
Copyright Year | 2016 |
Abstract | The G2 DNA damage checkpoint is one of the most important mechanisms controlling G2–mitosis transition. The kinase Greatwall (MASTL in human) promotes normal G2–mitosis transition by inhibiting PP2A via ARPP19 and ENSA. In this study, we demonstrate that MASTL is critical for maintaining genome integrity after DNA damage. Although MASTL did not affect the activation of DNA damage responses and subsequent repair, it determined the timing of entry into mitosis and the subsequent fate of the recovering cells. Constitutively active MASTL promoted dephosphorylation of CDK1Tyr15 and accelerated mitotic entry after DNA damage. Conversely, downregulation of MASTL or ARPP19/ENSA delayed mitotic entry. Remarkably, APC/C was activated precociously, resulting in the damaged cells progressing from G2 directly to G1 and skipping mitosis all together. Collectively, these results established that precise control of MASTL is essential to couple DNA damage to mitosis through the rate of mitotic entry and APC/C activation. |
Related Links | http://dx.doi.org/10.1038/srep22230 |
Starting Page | 22230 |
File Format | |
ISSN | 20452322 |
e-ISSN | 20452322 |
Journal | Scientific Reports |
Volume Number | 6 |
Language | English |
Publisher | Nature Publishing Group |
Publisher Date | 2016-02-01 |
Access Restriction | Open |
Rights Holder | Nature Publishing Group |
Subject Keyword | Science and technology Research in Higher Education |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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