Ben Van Houten

Address:
Hillman Cancer Center
5117 Centre Avenue
Research Pavilion, Suite 2.6
Pittsburgh, PA 15213-1863

Phone: 412--623-7762
Fax: 412-623-7761
Email: vanhoutenb@upmc.edu

PhD.: Oak Ridge Graduate School of Biomedical Science, University of Tennessee, 1984
Postdoc: Department of Biochemistry and the Lineberger Cancer Center, University of North Carolina at Chapel Hill.

Research:
Structure-function Studies of Nucleotide Excision Repair Proteins.
Faulty DNA repair can promote mutations, aging, cancer and cell death. The process by which protein components of repair detect damaged or modified bases within DNA is an important but poorly understood type of protein-DNA interaction. The cell contains a series of pathways designed to protect its DNA from environmental and endogenous damage. One of the most remarkable aspects of nucleotide excision repair (NER) is that it can remove a wide range of DNA lesions that differ in chemistry and structure. We are studying the structure, function and dynamics of bacterial NER proteins using a variety of approaches, including single-molecule techniques using Atomic Force microscopy, and TIRF microscopy. We seek to understand the structural motifs which these proteins use to recognize DNA damage and how these repair proteins sort through a sea of nondamaged DNA to find altered nucleotides.

Mitochondria and Disease:
Our group is testing the hypothesis that ROS generated in the mitochondria results in mtDNA damage causing a vicious cycle of damage: mtDNA damage causes a decrease in transcription and loss of essential mitochondrial proteins, causing a inhibition of electron transport and subsequent release in more ROS. This process causes further mitochondrial decline and many degenerative diseases associated with aging. We have developed a very sensitive DNA damage assay based on quantitative PCR that allows us to examine damage to nuclear and mitochondrial DNA from as little as 100 microliters of human blood. We are currently examining the role of mtDNA damage and repair in several human diseases including cancer and Friedreich’s ataxia. Finally, we are assessing the bioenergetics of cancer cells by measuring oxidative phosphorylation and glycolysis.

Recent Publications
J.H. Santos, J.N. Meyer, B.S. Mandavilli and B. Van Houten. (2006). Quantitative PCR-based measurement of nuclear and mitochondrial DNA damage and repair in mammalian cells. Methods Mol Biol. 314:183-99.

J. Truglio, E. Karakas, B. Rhau, H. Wang, M. DellaVecchia, B. Van Houten and C. Kisker. (2006). Structural basis of DNA damage recognition and processing by UvrB. Nature Structural & Molecular Biology. Mar 12; 13(4):360-4.

J.H. Santos, J.N. Meyer, and B. Van Houten. (2006). Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis Human Molecular Genetics 15(11):1757-68.

H.Wang, M. J. DellaVecchia, D. L. Croteau, and B. Van Houten. (2006) UvrB domain 4: an autoinhibitory gate for regulation of DNA binding and ATPase activity. J. Biol. Chem. 281(22):15227-37.

T.A. Kunkel and B. Van Houten. (2006). Survival choices. Nat Cell Biol.8(6):547-9.

D. L. Croteau, M. J. DellaVecchia, H. Wang, R. J. Bienstock, M. A. Melton, and B. Van Houten. (2006). The C-terminal zinc finger of UvrA regulates damage-specific DNA binding. J. Biol. Chem. Jul 7;. Sep 8;281(36):26370-81.

E. Karakas, J. J. Truglio, D. Croteau, B. Rhau, L. Wang, B. Van Houten and C. Kisker. (2007). Structure of the C-terminal half of UvrC reveals an RNase H endonuclease domain with an Argonaute-like catalytic triad. EMBO J 26(2):613-22.

J.N. Meyer, W.A Boyd, G.A Azzam, A.C. Haugen, A.C., Freedman, J.H., and B. Van Houten. (2007). Decline of nucleotide excision repair capacity in aging Caenorhabditis elegan.s Genome Biol. May 1;8(5):R70

Q. Ruan, T. Liu, A. Kolbanovskiy, Y. Liu, M. Skorvaga, Y. Zou, J. Lader, B. Malkani, S. Amin, B. Van Houten and N. E. Geacintov. (2007). Base sequence effect on nucleotide excision repair of a benzo[a]pyrene diol epoxide-N2-dG adduct catalyzed by thermophilic UvrABC proteins. Biochemistry. Jun 12;46(23):7006-15. Epub 2007 May 17.

M. J. DellaVecchia, W. K. Merritt, Y. Peng, T. W. Kirby, E. F. DeRose, G. A. Mueller, B. Van Houten, and R. E. London. (2007). NMR analysis of [methyl-13C]methionine UvrB from Bacillus caldotenax reveals UvrB-domain 4 heterodimer formation in solution. J. Mol. Biol. 373, 282�295.

D.L. Croteau, M.J. Dellavecchia, L. Perera, and B. Van Houten. (2008). Cooperative damage recognition by UvrA and UvrB: Identification of UvrA residues that mediate DNA binding. DNA Repair Mar 1;7(3):392-404.

S. Imoto, L.A. Bransfield, D.L. Croteau, B. Van Houten, and M.M. Greenberg. (2008). DNA tandem lesion repair by strand displacement synthesis and nucleotide excision repair. Biochemistry. Apr 8;47(14):4306-16. Epub Mar 15.

D.L. Croteau, Y. Peng, and B. Van Houten. (2008). DNA repair gets physical: Mapping an XPA-binding site on ERCC1. DNA Repair May 3;7(5):819-26. Epub Mar 14.

H. Wang, I. Tessmer, D.L. Croteau, D.A. Erie, and B. Van Houten. (2008). Functional Characterization and Atomic Force Microscopy of a DNA Repair Protein Conjugated to a Quantum Dot. Nano Lett. Apr 30.

S. C. Wolski, J. Kuper, P.H�nzelmann, J. Truglio, D. Croteau, B. Van Houten and C. Kisker (2008) . Crystal structure of the FeS cluster containing nucleotide excision repair helicase XPD. Plos Biology Jun 24;6(6):e149.

W. Ma, V. Panduri, J.F. Sterling, B. Van Houten, D.A. Gordenin, and M.A. Resnick. (2008). The transition of closely-opposed lesions to double-strand breaks during long-patch base excision repair is prevented by the coordinated action of DNA polymerase delta and Rad27/Fen1. Mol Cell Biol. 2008 Dec 15