Research Interests   Mechanisms of mammalian DNA double-strand break repair

Our objective is to gain an understanding of the molecular and biochemical mechanisms of mammalian DNA double-strand break (DSB) repair. The importance of DNA DSB repair is underscored by the existence of several human cancer predisposition diseases, such as Nijmegen chromosome breakage syndrome, ataxia telangiectasia and Fanconi's anemia, which are caused by defects in DNA repair. The high cancer rate associated with these and other human diseases suggests that generalized DNA repair is also critical for many other important biological processes including chromosome integrity and stability. In particular, we have recently shown that DNA DSB repair is required for telomere maintenance and have demonstrated that defects in DNA DSB repair genes leads to telomere dysfunction and genomic instability. Our basic experimental model system uses gene targeting techniques in human cell lines in culture. In summary, the identification and characterization of the genes and protein factors involved in DSB repair will provide insight into the general mechanisms of DNA recombination and DNA repair and could have therapeutic significance for many types of immune disorders and cancers.

Recent Publications
Ruis, B., Fattah, K. R., and Hendrickson, E. A. DNA-PKcs regulates proliferation, telomere length and genomic stability in human somatic cells. (2008) Mol. Cell. Biol., in press.

Fattah, F., Lichter, N., Fattah, K. R., Oh, S., and Hendrickson, E. A. Ku70, an essential gene, modulates the frequency of rAAV-mediated gene targeting in human somatic cells. (2008) Proc. Natl. Acad. Sci., USA, 105, 8703-8708. Cited as a Research Highlight in Nature Struct. Mol. Biol., (2008) 15:699.

Fattah, K., Ruis, B., and Hendrickson, E. A. Mutations to Ku reveal differences in human somatic cell lines. (2008) DNA Repair, 7, 762-774.

Hendrickson, E. A. Gene targeting in human somatic cells. (2008) In: Sourcebook of Models for Biomedical Research. M. Conn, Ed., Humana Press, Totowa, NJ, pp. 509-525 (REVIEW).

Ghosh, G., Li, G., Myung, K., and Hendrickson, E. A. The lethality of Ku86 (XRCC5) loss-of-function mutations in human cells is independent of p53 (TP53). (2007) Rad. Res., 167, 66-79.

Hendrickson, E. A., Huffman, J. and Tainer, J. A. Structural aspects of Ku and the DNA dependent protein kinase complex. (2006) In: DNA Damage Recognition. W. Seide, Y. W. Kow and P. W. Doetsch, Eds., Taylor & Francis Group, Inc., Boca Raton, FL, pp. 629-684 (REVIEW).

Myung, K., Ghosh, G., Fattah, F. J., Li, G., Kim, H., Dutia, A., Pak, E., Smith, S. and Hendrickson, E. A. Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86. (2004) Mol. Cell. Biol., 24, 5050-5059

Myung, K., Ghosh, G., Fattah, F. J., Li, G., Kim, H., Dutia, A., Pak, E., Smith, S. and Hendrickson, E. A. Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86. (2004) Mol. Cell. Biol., 24:5050-5059.

Hendrickson, E. A. , Huffman, J. and Tainer, J. A. Structural aspects of Ku and the DNA dependent protein kinase complex. (2005) In: DNA Damage Recognition. W. Seide, Y. W. Kow and and P. W. Doetsch, Eds., Marcel-Dekker, Inc., New York, NY, in press. (Review)

Braastad, C. D., Han, Z., and Hendrickson, E. A. Constitutive DNaseI hypersensitivity of p53-regulated promoters. (2003) J. Biol. Chem., 278:8261-8268.

Hu, X., Han, Z., Wyche, J. H., and Hendrickson, E. A. Helix 6 of tBid is necessary but not sufficient for mitochondrial binding activity. (2003) Apoptosis, 8:277-289.

Han, Z., Wei, W., Dunaway, S., Darnowski, J. W., Calabresi, P., Sedivy, J., Hendrickson, E. A., Balan, K., Pantazis, P., and Wyche, J. H. Role of p21 in apoptosis and senesence of human colon cancer cells treated with camptotehcin. (2002) J. Biol. Chem., 277:17154-60. (PubMed citation).

Braastad, C. D., Leguia, M, and Hendrickson, E. A. Ku86 autoantigen related protein-1 transcription initiates from a CpG island and is induced by p53 through a nearby p53 response element. (2002) Nucl. Acids Res, 30, 1713-1724. (PubMed citation).

Li, G., Nelsen, C., and Hendrickson, E. A. Ku86 is essential in human somatic cells. (2002) Proc. Natl. Acad. Sci., USA, 99, 832-837. (PubMed citation).

Han, Z., Pantazis, P., Wyche, J. H., Kouttab, N., Kidd, V. J. and Hendrickson, E.A. A FADD-dependent mechanism mediates the apoptotic action of non-steroidal anti-inflammatory drugs in the human leukemic Jurkat cell line. (2001) J. Biol. Chem., 276, 38748-38754. (PubMed citation).

Errami, A., Overkamp, W. J. I., He, D. M., Friedl, A. A., Gell, D. A., Eckardt-Schupp, F., Jackson, S. P. Hendrickson, E. A., Lohman, P. H. M., and Zdzienicka, M. Z. A new X-ray sensitive CHO cell mutant of ionizing radiation group 7, XR-C2, that is defective in DSB repair but has only a mild defect in V(D)J recombination. (2000) Mutat. Res., 461, 59-69. (PubMed citation).

Chatterjee, D., Pantazis, P., Li, G., Bremner, T. A., Hendrickson, E. A. and Wyche, J. H. Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptosis effector Bak. (2000) Oncogene, 19, 4108-4116. (PubMed citation).

Han, Z., Pantazis, P., Lange, T. S., Wyche, J. H. and Hendrickson, E. A. The staurosporine analog, Ro-31-8220, induces apoptosis independently of its ability to inhibit protein kinase C. (2000) Cell Death Diff., 7, 521-530. (PubMed citation).

Ihara, M., Suwa, A., Komatsu, K., Shimasaki, T., Okaichi, K., Hendrickson, E. A. and Okumura, Y. Heat sensitivity of double-stranded DNA-dependent protein kinase (DNA-PK) activity. (1999) Int. J. Radiat. Biol., 75, 253-258. (PubMed citation).