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At our laboratory, it has been studied how the genetic information is precisely transmitted from parents (parent cells) to offspring (daughter cells) and, conversely, which processes are involved in the mutation induced by inaccurate transmission of genetic information. We are also exercising our best efforts in education of young students highly interested in basic issues related to the DNA transaction and molecular mechanisms for evolution of organisms to help them become independent investigators.
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- Molecular mechanisms for mutation and its suppression (Fig. 1)
- Mechanisms for onset of DNA replication errors and mechanisms for their repair
- DNA damages due to oxygen radicals and its repair
- Molecular mechanisms for preservation and reorganization of chromosome and genome (Fig. 2)
- Control mechanisms for genetic recombination
- Roles of cell cycle checkpoint control
- Structures and function of DNA replicative apparatus (Fig. 3)
- Biochemical function of DNA polymerase
- Replication fork arrest and its recovery processes
Our studies, conducted to date, demonstrated that errors in DNA replication, that is, replication errors are the principal cause of small changes in DNA (point mutation) (Fig. 1). Another major cause of mutation is replication errors induced as a result of injury of DNA by oxygen radicals (those produced by oxygen respiration with cells). However, most of these replication errors and DNA lesions are eliminated in a sophisticated manner and with high efficiency by the numerous repair mechanisms possessed by cells (Figs. 1 and 2) and by the cell cycle checkpoint mechanism, resulting the incidence of mutation to be reduced to a very low level. Major changes on DNA such as deletion and chromosome reorganization play an important role in mutation, but their mechanism for onset has been clarified much less than the mechanism for point mutation.
We consider that “mechanism for precise transmission of genetic information” and “clarification of the mechanism for mutation” are indispensable for understanding the essential nature of organisms but are left almost unclarified. When approaching these questions, it is essential to deepen the insight into the function of DNA replicators (Fig. 3). Using E. coli and budding yeast mainly, we are actively engaged in multi-faceted studies with methods of molecular genetics and latest biochemical techniques (Fig. 4).
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- H. Maki, Annual Review of Genetics, 36, 279-303, 2002
- K. Higuchi et al., Genes to Cells, 8, 437-449, 2003
- T. Tsubota et al., Genes to Cells, 8, 873-888, 2003
- Y. Yagi et al., DNA Repair, 4, 1252-1269, 2005
- A. Sakai et al., Genes to Cells, 11, 767-778, 2006
- Tajima et al., J. Biol. Chem., 281, 32898-32908, 2006
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Fig. 1 Replication errors and natural spontaneous DNA lesion serve as major causes of mutation. Mutation by these factors is suppressed by multiple-stage mechanisms.
Fig. 2 If DNA is injured and DNA replication occurs without repair of the DNA lesion, the progression of replication forks is sometimes inhibited. Mechanisms available to avoid such inhibition (i.e., post-replication repair) include recombinant repair, regression of replication forks and translesion DNA synthesis.
Fig. 3 In eukaryotic DNA replication forks, three types of DNA polymerase ordinary work together for efficient DNA replication, thus reducing the incidence of replication errors low. Special bypass DNA polymerase works in both eukaryote and bacteria when the replication fork is stopped by DNA lesion.
Fig. 4 Diverse studies are being conducted, using Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae (budding yeast) and Xenopus laevis.
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