Tadahime Izumi        

tadahime izumi

Research Interests

The research interests of Izumi lab include mechanisms of cellular defense and DNA repair against the DNA damage and mutagenesis, specifically those generated by reactive oxygen species (ROS).  Apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA base excision repair (BER) protein that is arguably rate limiting for overall repair of DNA single-strand breaks (SSBs) generated by oxidative stress and alkylating reagents. BER by APE1 and other key repair proteins, including XRCC1 (X-ray cross complementation group 1 gene) and PARP (poly (ADP-ribose)polymerase), is thus a mechanism to prevent mutagenesis and carcinogenesis caused by endogenous oxidative stress.  However, a less appreciated fact is that once mutations are fixed and cells are transformed, BER becomes harmful due to its protective role in tumor cells against chemo- and radiation-therapy (CRT).  Tumors of the head and neck (HN) as well as brain that are CRT-resistant tend to show a higher level of APE1 than normal tissues.  Understanding the regulatory mechanism of this important BER enzyme in the cells, by protein-protein and DNA-protein interactions, should thus provide information critical for a better cancer treatment.

Selected publications

  1. Peddi, S.R., Chattopadhyay, R., Naidu, C.V., Izumi, T. (2006) The Human Apurinic/Apyrimidinic Endonuclease-1 Suppresses Activation of Poly(ADP-ribose) Polymerase-1 Induced By DNA Single Strand Breaks. Toxicology, 224, 44-55.
  2. Chattopadhyay, R., Wiederhold, L., Szczesny, B., Boldogh, I., Hazra, T.K., Izumi, T., Mitra, S. (2006) Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells. Nucleic Acids Res., 34, 2067-2076
  3. Jackson, EB, Theriot, C.A., Chattopadhyay, R., Mitra, S., T. Izumi (2005) Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1).  Nucleic Acids Res. 33:3303-3312.
  4. Izumi, T., Brown, D.B., Naidu, C.V., Bhakat K.K., MacInnes M.A., Saito H.., Chen, D.J., Mitra, S. (2005) Two essential but distinct functions of the mammalian AP endonuclease 1.  Proc. Natl. Acad. Sci. USA 102: 5739-5743.
  5. Wiederhold, L., Leppard, J.B., Kedar, P., Karimi-Busheri, F., Rasouli-Nia, A., Weinfeld, M., Tomkinson, A.E., Izumi, T., Prasad, R., Wilson, S.H., Mitra, S., Hazra, T.K. (2004) AP endonuclease-independent DNA base excision repair in human cells.  Mol. Cell, 15, 209-220.
  6. Izumi, T., Schein, C.H., Oezguen, N., Feng, Y., Braun, W. (2004) Effects of backbone contacts 3' to the abasic site on the cleavage and the product binding by human apurinic/apyrimidinic endonuclease (APE1). Biochemistry, 43: 684-689.
  7. Bhakat, K., Izumi, T., Yang, S., Hazra, T., and Mitra, S. (2003) Role of acetylated human AP-endonuclease (APE1/Ref1) in regulation of the parathyroid hormone gene.  EMBO J, 22: 6299-6309.
  8. Izumi. T., Wiederhold, L.R., Roy, G., Roy, R., Jaiswal, A., Bhakat, K.K., Mitra, S., Hazra, T.K. (2003) Mammalian DNA base excision repair proteins: their interactions and role in repair of oxidative DNA damage. Toxicology, 193: 43-65.
  9. Hazra, T.K., Kow, Y.W., Hatahet, Z., Imhoff, B., Boldogh, I., Mokkapati, S.K., Mitra, S., and Izumi, T. (2002) Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions., J. Biol. Chem. 277: 30417-30420.
  10. Hazra, T.K., Izumi, T., Boldogh, T., Imhoff, B., Kow, Y.W., Jaruga, P., Dizdaroglu, M., and Mitra, S. (2002) Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA, Pro. Natl Acad Sci USA, 99:3523-3528
  11. Kuninger, D.K., Izumi, T., Papaconstantinou, J., and Mitra, S. (2002) Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease-1 promoter, Nucleic Acids Res., 30:823-829.
  12. Izumi, T., Hazra, T.K., Bolodogh, I., Park, M.S., Tomkinson, A., Park, M.S., Ikeda, S., and Mitra,S. (2000) Requirement of human AP-endonuclease in repair of DNA single-strand breaks by reactive oxygen species. Carcinogenesis 21: 1329-1334
  13. Mol, C.D., Izumi, T., Mitra, S., and Tainer, J.A. (2000) Human APE1:DNA structures and mutants reveal abasic DNA binding to stage DNA repair. Nature 403: 451-456.
  14. Izumi, T., Malecki, J., Chaudhry, M. A., Hill, J. W., Weinfeld, M., Lee, J. C., and Mitra, S. (1999) Intragenic suppression of an active site mutation in the human apurinic/apyrimidinic endonuclease.  J. Mol. Biol. 287: 47-57.
  15. Johnson, R. E., Torres-Ramos, C. A., Izumi, T., Mitra, S., Prakash, S., and Prakash, L. (1998) Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites  Gene. Dev. 12: 3137-3143.

Contact: tizumi@lsuhsc.edu