Research Program: Genetic Mechanisms of Cancer
Professor, Department of Biochemistry, Molecular Biology & Biophysics

hendr064@umn.edu
612-624-5988 — office
612-624-0935 — lab
Preferred method of contact: e-mail

Dr. Hendrickson received his Ph.D. from Harvard Medical School in 1987. He conducted his postdoctoral research in the the Dana Farber Cancer Institute/Harvard Medical School.

Research Interests

Our objective 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 a pathway of DSB repair called non-homologous end joining (NHEJ) and the complex, DNA-dependent protein kinase, that regulates this pathway. NHEJ is essential for two overlapping processes: lymphoid V(D)J recombination and resistance to DNA damage. The relatedness of DNA DSB repair to V(D)J recombination and DNA damage is underscored by the existence of several human immune deficiency/chromosome breakage syndromes, such as Nijmegen breakage syndrome, familial predisposition to breast cancer, ataxia telangiectasia-like disorder and Fanconi's anemia. Affected individuals are generally 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 DNA-dependent protein kinase and NHEJ are integrally related to telomere maintenance. Experimentally, the laboratory makes use of recombinant adenoviral associated virus (rAAV) to knock out or modify genes at high frequency in human somatic cells. 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 and is also relevant to improving methods of gene therapy.

Selected Publications

Han Z, Pantazis P, Wyche JH, Kouttab N, Kidd VJ, Hendrickson EA. A Fas-associated death domain protein-dependent mechanism mediates the apoptotic action of non-steroidal anti-inflammatory drugs in the human leukemic Jurkat cell line. J Biol Chem. 2001;276:38748-38754.

Li G, Nelsen C, Hendrickson EA. Ku86 is essential in human somatic cells. Proc Natl Acad Sci. USA 2002;99:832-837.

Braastad CD, Leguia M, Hendrickson EA. Ku86 autoantigen related protein-1 transcription initiates from a CpG island and is induced by p53 through a nearby p53 response element. Nucl Acids Res. 2002;30:1713-1724.

Braastad CD, Han Z, Hendrickson EA. Constitutive DNaseI hypersensitivity of p53-regulated promoters. J Biol Chem.2003;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. Apoptosis 2003;8:277-289.

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

Ghosh G, Li G, Myung K, Hendrickson EA. The lethality of Ku86 (XRCC5) loss-of-function mutations in human cells is independent of p53 (TP53). Radiat Res. 2007;167:66-79.

Hendrickson, E. A., Huffman, J. and Tainer, J. A. Structural aspects of Ku and the DNA dependent protein kinase complex. In: DNA Damage Recognition. Seide W, Kow YW, Doetsch PW, Eds., Marcel-Dekker, Inc., New York, NY, 2006; 596-641.

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

Fattah K, Ruis B, and Hendrickson EA. Mutations to Ku reveal differences in human somatic cell lines. DNA Repair 2008;7:762-774.

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

Ruis B, Fattah KR, and Hendrickson EA. DNA-PKcs regulates proliferation, telomere length and genomic stability in human somatic cells. Mol Cell Biol. 2008; in press.