In our laboratory, we are working on chromosome dynamics, cell cycle regulation, and epigenetics in fission yeast and liverwort. For example, the projects such as “Regulation of chromosomal functions by SUMO modification”, “Genome integrity checkpoints”, and “Molecular mechanism of RNA interference (RNAi)” are in progress.

Project 1. Regulation of chromosomal functions by SUMO modification

SUMOylation, the covalent attachment of a Small Ubiquitin-like Modifier (SUMO) to target proteins, plays important roles in a wide variety of cellular functions, including DNA repair, cell cycle progression, and chromatin dynamics. We have shown that, in fission yeast, mutations of SUMO (Pmt3) leads to longer telomeres in a telomerase-dependent manner. We have recently established Tpz1-K242 SUMOylation as a critical regulatory mechanism that connects shelterin and Stn1-Ten1 complexes to regulate telomere homeostasis in fission yeast. Now we are trying to understand how SUMOylation regulates chromosomal functions in more detail.

Project 2. Genome Integrity Checkpoints

Eukaryotic cells have developed sophisticated surveillance mechanisms called checkpoints to regulate responses to DNA damage and perturbations of DNA replication. The failure of a checkpoint can be potentially catastrophic, leading to an elevated mutation rate, chromosome instability, and the development of cancer. There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. We are analyzing the multiple functions and the regulation of the S-phase checkpoint mediator in fission yeast.

Project 3. Molecular mechanism of RNA interference (RNAi)

Regulation of eukaryotic DNA transcription is classified into two regulations. One regulation is managed by many transcriptional factors that bind DNA in a sequence-dependent manner. The other regulation is sequence-independent, called epigenetics. RNA interference (RNAi) pathway is involved in epigenetics, small RNAs generated in this pathway repress gene expression.

Heterochromatin is the chromosomal region that covered with methylated histone proteins and always repressed gene expression, required for proper chromosome segregation and stability. We are interested in the mechanism of regulation of RNAi-mediated transcriptional states. We are currently studying how RNAi promotes the modification of histones at heterochromatin in fission yeast.