Laboratories and faculty

Microbial Molecular Genetics

Prof. Maki Assoc prof. Akiyama
Hisaji MAKI
Associate Professor
Masahiro AKIYAMA
Labs HP

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).

Fig. 1
Fig. 1 Multiple mechanisms suppress mutations. However, spontaneous DNA lesions serve as major causes of mutation under normal growth conditions.
Fig. 2
Fig. 2 When DNA replication occurs without repair of DNA lesions, replication fork progression is inhibited, potentially leading to genetic instability. Mechanisms to rescue arrested forks include recombination, regression of forks and translesion DNA synthesis.
Fig. 3
Fig. 3 Multiple DNA polymerases ordinarily work together for efficient DNA replication, thereby suppressing replication errors. Special DNA polymerases work in both eukaryote and bacteria to copy damaged DNA (translesion DNA synthesis).
Fig. 4
Fig. 4 (A) Counting of mutant cell numbers to study spontaneous mutations of E. coli, (B) Purification of replication enzymes for authentic biochemistry, (C) Microscopic image of E. coli cells and (D) Investigation of replication fork speed in E. coli cells


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  2. K. Higuchi et al., Genes to Cells, 8, 437-449, 2003
  3. A. Sakai et al., Genes to Cell, 11, 767-778, 2006
  4. K. Hasegawa et al., Genes to Cells, 13, 459-469, 2008
  5. A. Furukohri et al., J. Biol. Chem., 283, 11260-11269, 2008
  6. K. Uchida et al., Mol. Microbiology, 70, 608-622, 2008
  7. S. Ide et al., Science, 327, 639-696, 2010
  8. A. Furukohri et al., Nucleic Acid Res., 40, 6039-6048, 2012
  9. T.M. Pham et al., Mol. Microbiology, 90, 584-596, 2013
  10. M. Ikeda et al., Nucleic. Acid Res., 42, 8461-8472, 2014
  11. H.P. Le et al., Genes Cells, 20, 817-33, 2015
  12. C.T. Lim et al., Nucleic. Acid Res., 43, 9804-16, 2015
  13. K.W. Tan et al., Nucleic. Acid Res., 43, 1714-25, 2015
  14. P.J. Lai et al., Genes Cells, 21, 136-45, 2016
  15. M.T. Akiyama et al., Genes Cells, 21, 907-914, 2016