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 - Radiation Biology Center
Genome Dynamics (Laboratory of Genome Dynamics)
Current work in radiation biology, which started from the identification and isolation of genes responsible for radiation-sensitive human diseases, has revealed that the proteins which have a role in cellular radiation responses are also involved in a variety of important biological processes such as homologous recombination, DNA replication, cell cycle checkpoints, telomere maintenance. Our group is pursuing studies of repair gene networks starting with a NBS1 gene found to be responsible for a radiation sensitive disease. We would like to welcome serious students to join us if they are interested in helping to develop this new field of modern radiation biology.

  Kenshi Komatsu, Ph.D.
Professor
Research and Education
Our group is focusing on the biology of one protein in order to understand its multifunctional behavior in responding to DNA double-strand breaks, and the relationship of these breaks to a variety of pathways in living cells. Nijmegen breakage syndrome, characterized by a high sensitivity to DNA double-strand breaks and a predisposition to cancer, is a rare recessive genetic disease. NBS1, the underlying gene responsible for this disease, initiates homologous recombination repair in DNA by recruiting the Mre11/Rad50 nuclease to sites of DNA damage. NBS1 is also involved in cell growth and division through its regulation of S-phase and G2-phase checkpoints. Since damage repair is coordinated with cell growth, communication between DNA repair and checkpoint regulation functions is being investigated by the analysis of histone modifications. This modification process appears to be a unifying agent for the understanding of genome network function. Homologous recombination, initiated by the NBS1 gene, is an essential event for repair and meiotic recombination, and is also essential for the development of recombinant proteins, and thus another goal of our work is to understand the multiple pathways involved in homologous recombination and its regulation. Biological phenomena in living cells cannot be studied today by assigning each problem into a specific research area, and most problems studied today will be of interest or relevance to several different fields. Modern radiation biology is multidisciplinary area. Our goal of education is to support young scientists who take a multidisciplinary approach, and try to understand real biological events with the tools and methods available from a number of modern fields.


Genome Dynamics
Radiation Biology Center
Professor Kenshi Komatsu
Associate
 Professor


Junya Kobayashi
TEL +81-75-753-7550
FAX +81-75-753-7564
e-mail komatsuhouse.rbc.kyoto-u.ac.jp
URL http://www.rbc.kyoto-u.ac.jp/Genome/index.html
NBS1, the product of the gene underlying the Nijmegen breakage syndrome, contains three functional regions: the forkhead associated (FHA) domain and CA1 C-terminus (BRCT) domain at the N-terminus, several SQ motifs (consensus phosphorylation sites by ATM and AT kinases) at a central region and MRE11-binding region at the C-terminus. The orthologs of NBS1 have not been identified in prokaryotes or archaebacteria, suggesting that this protein, especially the N-terminus, is unique to eukaryotic cell functions.
NBS1 forms a multimeric complex with hMRE11/hAD50 nuclease at the C-terminus and recruits or retains them at the vicinity of sites of DNA damage by direct binding to histone H2AX, which is phosphorylated by ATM in response to DNA damage. Thereafter, the NBS1-complex proceeds to rejoin double-strand breaks predominantly by homologous recombination repair and this process collaborates with cell-cycle checkpoints to facilitate DNA repair. The immunofluorescent staining indicated co-localization of gamma-H2AX foci and hME11 foci formation in wild type cells (low panel), but hMRE11 protein was confined in cytoplasm in NBS cells (upper right).
Laboratory staffs
Recent Publications
1. Nakamura K, Kato A, Kobayashi J, Yanagihara H, Sakamoto S, Oliveira DV, Shimada M, Tauchi H, Suzuki H, Tashiro S, Zou L, Komatsu K (2011) Regulation of homologous recombination by RNF20-dependent H2B ubiquitination. Mol Cell, 41:515-28.
2. Yanagihara H, Kobayashi J, Tateishi S, Kato A, Matsuura S, Tauchi H, Yamada K, Takezawa J, Sugasawa K, Masutani C, Hanaoka F, Weemaes CM, Mori T, Zou L, Komatsu K (2011) NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis. Mol Cell, 43: 788-797
3. Tauchi H, Kobayashi J, Morishima K, van Gent DC, Shiraishi T, Verkalk NS, van Heems D, Itoh E, Nakamura A, Sonoda E, Takata M, Takeda S, Matsuura S, Komatsu K (2002) Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells, Nature, 420:93-98.