Update: 24 January 2012
It is the glory of God to conceal a matter; to search out a matter is the glory of kings.
Current interest of the lab is on DNA damage and the related cellular responses. Major topics are the following:
Direct Involvement of p53 in the Nucleotide Excision Repair (NER)
Tumor suppressor p53, a well-known transcription activator, enhances DNA repair. This enhancement may be dependent or independent on p53 transactivation. Our study suggests that p53 protein is required for recruitment of XPB and RPA to DNA damage site. The amino acid sequences 299-308 of p53 protein are crucial in this regard.
(1 h after local UV irradiation; probed with anti-CPD or anti-RPA antibodies)
Inhibition of the rejoining of NER by subsequent base excision repair
We have found that agents which induce oxidative DNA damages such as amoxicillin (an antibiotic), propolis (natural product of beehives) and colcemid (a spindle inhibitor) perturb the rejoining of NER. This is considered as consequence of the competition for repair resources between NER and base excision repair.
Mechanism of cellular adaptation to oxidative stress
A brief oxidative stress caused by agents such as propolis renders cells to resist the second challenge of the kind; the phenomenon we call it adaptation. De novo synthesis of protein is necessary for the adaption. Proteomic analysis is under investigation for revealing the underlying mechanism.
(C: Control; HX: cycloeximide; C and prop: without or with pre-treatment of propolis)
Tsai, Y.C., Wang, Y.S., Liou, CC. and Liu, Y.C. (2012) Induction of oxidative DNA damage by flavonoids of propolis: Its mechanism and implication about antioxidant capacity. Chemical Research in Toxicology 25: 191−196 .
Chen, M.K., Tsai, Y.C., Li, P.Y., Liou, J.C. Taniga E.S., Chang, D. W., Mori, T. and Liu, Y.C. (2011) Delay of gap filling during nucleotide excision repair by base excision repair: The concept of competition exemplified by the effect of propolis. Toxic. Sci. 122:339-348.
Nishiwaki T, Kobayashi N, Iwamoto T, Yamamoto A, Sugiura S, Liu Y.C., Sarasin A, Okahashi Y, Hirano M, Ueno S, Mori T (2008) Comparative study of nucleotide excision repair defects between XPD-mutated fibroblasts derived from trichothiodystrophy and xeroderma pigmentosum patients. DNA Repair 7:1990-1998.
Chang, Y.C., Liao, C.B., Chiang-Hsieh, P.Y., and Liu, Y.C. (2008) Expression of tumor suppressor p53 facilitates DNA repair but not UV-induced G2/M arrest or apoptosis in Chinese hamster ovary CHO-K1 cells. J. Cell Biochem 103:528-537.
Liao, C.B., Chang, Y.C., Kao, C.W., Taniga E.S., Li, H., Tzang, B.S. and Liu, Y.C. (2006) Deregulation of cyclin-dependent kinase 2 activity correlates with UVC- induced apoptosis in Chinese hamster ovary cells. J. Cell Biochem. 97:824-35.
Li, H., Chang, T.W., Tsai, Y.C., Chu, S. F., Wu, Y.Y., Tzang, B.S. Liao, C.B. and Liu, Y.C. (2005) Colcemid inhibits the rejoining of the nucleotide excision repair of UVC-induced DNA damages in Chinese hamster ovary cells. Muta. Res. 88:118-128.