Name Akimitsu Konishi, M.D., Ph.D.Affiliation Medical Top Track (MTT) Program
Title Junior MTT Fellow
Subjects of Research
1. Understanding of DNA damage signaling
2. Mechanism of the chromosome end protection
Research Summary
The biological response to DNA damage is one of the central issues in modern biology. The continuity of life depends on the ability of cells to protect their DNA from intrinsic and extrinsic damage and deficiencies in the DNA damage response can contribute to tumorigenesis, aging, hereditary disorder, and fertility problems. Eukaryotic chromosomes end in specialized structures, called telomeres, to cap chromosomal ends, preventing induction of DNA damage response. Our group studies DNA damage signaling using the dysfunctional telomere as a tool. We have identified a temperature-sensitive allele of TRF2, key protective factor at telomere. Using this system, we can control the generation of DNA damage at telomeres.
Publications
1. Niida H, Tsuge S, Katsuno Y, Konishi A, Takeda N, Nakanishi M. Depletion of Chk1 leads to premature activation of Cdc2-cyclin B and mitotic catastrophe. J Biol Chem. 280(47): 39246-52 (2005)
2. Konishi A, Shimizu S, Hirota J, Takao T, Fan Y, Matsuoka Y, Zhang L, Yoneda Y, Fujii Y, Skoultchi AI, Tsujimoto Y. Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. Cell.114(6): 673-88 (2003)
3. Shimizu S, Konishi A, Kodama T, Tsujimoto Y. BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death. Proc Natl Acad Sci USA. 97(7):3100-5 (2000)
Experimental techniques
1. Analysis of telomeric and chromosomal abnormalities
2. Gene engineering & handling of virus vector
3. Various biochemical techniques
(protein purification etc.)
(protein purification etc.)