Research summary

Our goal is to understand the molecular mechanisms responsible for faithful inheritance of genetic materials and stable maintenance of the genome. In particular, we focus on elucidating regulatory mechanisms for DNA replication in E. coli, fission yeast, and mammalian cells. Understanding how chromosomes are replicated and inherited will allow us to determine how defects in these processes cause diseases, such as cancers, or lead to cellular senescence. From our studies, we are aiming to identify novel target proteins for cancer treatments or amelioration of age-associate phenotypes. Specific questions we are addressing are :

• 1) How is the timing and location of DNA replication determined, and how are these coordinated with other chromosomal processes?
• 2) How do G-quadruplex structures regulate DNA regulation and chromosome architecture?
• 3) How do various biological stresses induce replication checkpoint and how does it affect genome stability and potentially cause cancer?
• 4) What are the roles of replication and checkpoint factors in developmental processes?
• 5) How have replication systems evolved and diversified in response to changing environments?
• 6) How can we develop effective cancer therapies targeting replication/ checkpoint factors?

A model for chromatin compartmentalization generated by Rif1 near nuclear periphery.

Rif1 protein binds to G4 structures in chromatin and promotes chromatin loop formation through oligomerization. Rif1 also binds to nuclear membranes either directly or through lipid modification, tethering chromatin fibers to the nuclear periphery. It can also induce compartmentalization through liquid-liquid phase separation to generate confined, but dynamic and interactive chromatin compartments.