Unknown

Dataset Information

0

MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation.

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 CDK1(Tyr15) 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.

SUBMITTER: Wong PY 

PROVIDER: S-EPMC4770598 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation.

Wong Po Yee PY   Ma Hoi Tang HT   Lee Hyun-jung HJ   Poon Randy Y C RY  

Scientific reports 20160229

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 recove  ...[more]

Similar Datasets

Unknown Dephosphorylation of Plk1 occurs through PP2A-B55/ENSA/Greatwall pathway during mitotic DNA damage recovery.
| S-EPMC6592230 | biostudies-literature
Unknown Greatwall and Polo-like kinase 1 coordinate to promote checkpoint recovery.
| S-EPMC3190707 | biostudies-literature
Unknown Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer.
| S-EPMC5943447 | biostudies-literature
Unknown Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry.
| S-EPMC4792957 | biostudies-literature
Unknown DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint.
| S-EPMC545827 | biostudies-other
Unknown Implications of alternative routes to APC/C inhibition by the mitotic checkpoint complex.
| S-EPMC6157902 | biostudies-literature
Unknown CDK1 regulates mediator of DNA damage checkpoint 1 during mitotic DNA damage.
| S-EPMC3488166 | biostudies-literature
Unknown Defining the role of APC in the mitotic spindle checkpoint in vivo: APC-deficient cells are resistant to Taxol.
| S-EPMC3016607 | biostudies-literature
Unknown Degradation of the human mitotic checkpoint kinase Mps1 is cell cycle-regulated by APC-cCdc20 and APC-cCdh1 ubiquitin ligases.
| S-EPMC2963336 | biostudies-literature
Unknown Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression.
| S-EPMC8042607 | biostudies-literature