ERIC HENDRICKSON

Associate Professor
Graduate Program in Molecular and Cell Biology and Biochemistry
Ph.D., Harvard University, 1987
(401) 863-3667

[email protected]

Research Summary

The objective of my laboratory is to gain an understanding of the molecular and biochemical mechanisms of mammalian DNA double-strand break (DSB)repair. In particular, my laboratory is studying two overlapping processes integral to DSB repair: lymphoid V(D)J recombination and X-ray sensitivity. The relatedness of DNA DSB repair to V(D)J recombination and X-ray sensitivity is underscored by the existence of several human immune deficiency/chromosome breakage syndromes, such as Bloom's syndrome, ataxia telangiectasia and Fanconi's anemia. Affected individuals are characterized by having impaired immune capabilities, suspected defects in DSB repair and a greatly elevated incidence of cancer. The high cancer rate associated with these human diseases suggests that generalized DSB repair is also critical for many other important biological processes including chromosome integrity and stability, mutagenesis and carcinogenesis as well as lymphoid V(D)J recombination. In particular, we have also recently shown that DSB repair is integrally related to apoptosis. 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.

Selected Publications

Han, Z., Malik, N., Carter, T., Reeves, W. H., Wyche, J. H., and Hendrickson, E. A. DNA-dependent protein kinase is a target for a CPP32-like apoptotic protease. (1996) J. Biol. Chem., 271, 25035-25040.
Lee, S. E., Mitchell, R. A., Cheng, A., and Hendrickson, E. A. Evidence for DNA-PK dependent and independent DNA double strand break repair pathways in mammalian cells as a function of the cell cycle. (1997) Mol. Cell. Biol., 17, 1425-1433.
Myung, K., He, D. M., Lee, S. E. and Hendrickson, E. A. KARP-1: A novel leucine zipper protein expressed from the human Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. (1997) EMBO J., 16, 3172-3184.
Hendrickson, E. A. Cell cycle regulation of mammalian DNA double-strand break repair. (1997) Amer. J. Hum. Genet., 61, 795-800 (review).
Myung, K., Braastad, C., He, D. M. and Hendrickson, E. A. KARP-1: a p53-dependent link between ataxia telangiectasia and DNA-dependent protein kinase. (1998) Proc. Natl. Acad. Sci. USA, 95, 7664-7669.
Han, Z., Li, G., Bremner, T. A., Lange, T. S., Zhang, E. G., Jemmerson, R., Wyche, J. H. and Hendrickson, E. A. A cytosolic factor is required for mitochondrial cytochrome c efflux during apoptosis. (1998) Cell Death Diff., 5, 469-479.
Han, Z., Bhalla, K., Pantazis, P., Hendrickson, E. A. and Wyche, J. H. Cif (Cytochrome c-efflux inducing factor) activity is regulated by Bcl-2 and caspases and correlates with the activation of Bid. (1999) Mol. Cell. Biol., 19, 1381-1389.
Sedivy, J. M., Vogelstein, B., Liber, H. L., Hendrickson, E. A. and Rosmarin, A. Gene targeting in human cells without isogenic DNA. (1999) Science, 283, 9a.
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.

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