Outline of Research and Education
At our laboratory, we have been studying how genetic information is precisely transmitted from parent cells to daughter cells and, conversely, how mutation is induced by inaccurate transmission of genetic information. To approach these questions, it is important to understand molecular mechanisms of genomic stability and molecular functions of DNA replication machineries. We also put strong emphasis on the international education of young students who are highly interested in basic issues related to DNA transaction (3R: Replication, Repair and Recombination) and the molecular mechanisms of biological evolution. We want to assist our laboratory members in becoming globally active individuals who act and think independently.
Major Research Topics
Mechanisms of spontaneous mutation and its suppression (Fig.1)
- Onset of DNA replication errors and their repair (References 1 & 4)
- Generation of DNA damage due to oxygen radicals and its repair (References 1 & 3)
- Spontaneous mutation induced by cellular growth environments
Molecular mechanisms for genetic stability (Fig.2)
- Control mechanisms for genetic recombination
- Roles of DNA damage response and cell cycle checkpoint control (Reference 7)
Molecular functions of DNA replication machineries (Fig.3)
- Biochemical activities of DNA polymerases (References 2, 5, 8, 10-12 & 14)
- Replication fork arrest and its recovery processes (Reference 10)
- Dynamics of replication fork movement on genomes (References 6, 9, 13 & 15)
Errors caused by DNA polymerase, that is, “replication errors” are thought to be the principal source of small changes (point mutations) in DNA (Fig.1). “DNA damage” is also considered to be another cause of mutation. Our studies, conducted to date, demonstrated that most of these replication errors and DNA lesions are efficiently eliminated by the numerous cellular repair mechanisms (Fig.1 & 2), resulting the incidence of “spontaneous mutation” (rare mutations caused in natural environments) to be reduced to a very low level under normal growth conditions. We found that oxidative DNA damage and errors in repair DNA synthesis mainly contribute to rare spontaneous mutations (references 1, 2 and 3).
We consider that elucidation of “mechanism for faithful transmission of genetic information” and “mechanism for spontaneous mutation” (Fig.4A) is crucial to understand the essential nature of organisms but is left almost unresolved. When approaching these, it is also essential to get better insight into molecular functions of replication enzymes in vitro (Fig.3; references 4 and 5) and dynamics of replication forks in vivo (Fig.4D; reference 6). Using E. coli (Fig.4C), we are actively engaged in studies of these subjects with methods of modern molecular genetics and authentic biochemistry (Fig.4B).
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