Spatiotemporal regulation of the Dma1-mediated mitotic checkpoint coordinates mitosis with cytokinesis

Abstract

During cell division, the timing of mitosis and cytokinesis must be ordered to ensure that each daughter cell receives a complete, undamaged copy of the genome. In fission yeast, the septation initiation network (SIN) is responsible for this coordination, and a mitotic checkpoint dependent on the E3 ubiquitin ligase Dma1 and the protein kinase CK1 controls SIN signaling to delay cytokinesis when there are errors in mitosis. The participation of kinases and ubiquitin ligases in cell cycle checkpoints that maintain genome integrity is conserved from yeast to human, making fission yeast an excellent model system in which to study checkpoint mechanisms. In this review, we highlight recent advances and remaining questions related to checkpoint regulation, which requires the synchronized modulation of protein ubiquitination, phosphorylation, and subcellular localization.

Catalysis-dependent and redundant roles of Dma1 and Dma2 in maintenance of genome stability in Saccharomyces cerevisiae

“…While Dma1 and Dma2 have been shown to play an important role in degradation of Swe1, regulation of cell cycle, G1 cyclin degradation and septin dynamics, (45,49,(73)(74)(75), their role on chromatin has never been addressed. Here, we show that Dma1 and Dma2 interact with histones and Rad53 and are localized to gene bodies in a manner similar to the established localization of RNAPII and various other components of transcription machinery (76), indicating that Dma1 and Dma2 may play a role in maintenance of genome stability during transcription elongation.…”

The Functions of DNA Damage Factor RNF8 in the Pathogenesis and Progression of Cancer

“…This requires the appropriate coordination of mitosis with cytokinesis, the final event of cell cycle that occurs concurrently with mitosis. Failure of mitotic checkpoint and cytokinesis can result in genomic instability which contributes to cancer development [52,53]. RNF8 also participates in maintaining genomic stability by regulating mitosis and cytokinesis.…”

Altered cohesin dynamics and histone H3K9 modifications contribute to mitotic defects in thecbf11Δlipid metabolism mutant

“…Mitotic defects can result in aneuploidy, as frequently seen in cancer cells, or in catastrophic mitosis and cell death. As such, mitosis is tightly controlled and regulated at many different levels (Bähler, 2005; Cullati and Gould, 2019; Grallert et al, 2015). The fission yeast Schizosaccharomyces pombe has been instrumental in identifying the factors and processes involved in mitosis, and in defining their effects on mitotic fidelity (Hayles and Nurse, 2018; Hayles et al, 2013).…”