Our laboratory is interested in the mechanism of maintenance DNA methylation during cell proliferation. DNA methylation is one of the best known epigenetic modifications and plays an essential role in many biological events such as transcriptional regulation, development, differentiation, suppression of retrotransposons, and maintenance of genome stability. Therefore, the DNA methylation pattern needs to be accurately inherited to daughter DNA when the replication of genomic DNA occurs, and dysregulated DNA methylation causes various diseases including cancer. However, we still do not know the entity of the molecular mechanism maintaining the DNA methylation pattern, due to its complexity. Particularly, it is unclear what triggers the collapse of maintenance DNA methylation machinery and, consequently, genome instability or diseases. To answer this critical question, we utilize a cell-free system that can reproduce the chromosomal replication in vitro to advance our research. Besides, we aim to develop novel DNMT inhibitors based on the new molecular mechanisms that we discovered. In addition, in our laboratory, we are exploring the molecular basis of tumorigenesis and aging. For more information on our laboratory, please visit our homepage. http://www.ims.u-tokyo.ac.jp/cancer-cell-biology/hp2018/01index.html