Bennet Van Houten
Richard M. Cyert Professor of Molecular Oncology, The University of Pittsburgh's Department of Pharmacology and Chemical Biology
Co-Leader, Program of Molecular and Cellular Cancer Biology, University of Pittsburgh Cancer Institute
Associate Director for Basic Research, Aging Institute, University of Pittsburgh
Research
Research in the Van Houten laboratory is in two general areas: 1) mitochondrial function and disease and 2) analysis of DNA nucleotide excision repair enzymes by single molecule techniques. The goal of the DNA repair experiments is to examine repair in real-time at the single molecule level using DNA protein-quantum dot (Qdot) conjugates. We have initiated single-molecule imaging of repair protein dynamics using atomic force microscopy (Nano Letters, 2008) and single-molecule fluorescence using quantum dot conjugated bacterial and human proteins (Molecular Cell, 2010; Nucleic Acids Res. 2013; PNAS, 2012, 2014,). Together these studies help demonstrate the dynamic hand off of processed DNA lesions from one repair protein to another.Publications
Kad, N.; Van Houten, B. Single molecule techniques in DNA repair: A primer. Special Issue of DNA Repair (in press). 2014.
Kad, N.; Van Houten, B. Investigation of bacterial nucleotide excision repair using single-molecule techniques. Special Issue of DNA Repair (in press). 2014, PMID:24472181. PMCID:PMC Journal.
Ghodke, H.; Wang, H.; Hsieh, C. L; Woldemeskel, S.; Watkins, S.; Rapic-Otrin, V.; Van Houten, B. Single molecule analysis of the human repair protein, UV-damaged DNA binding protein (UV-DDB), reveals a complex kinetic landscape for the formation of long-lived (DDB1-DDB2)2 dimers at sites of DNA damage. PNAS Plus (in press). 2014, May 6;111(18):E1862-71. doi: 10.1073/pnas.1323856111. Epub 2014 Apr 23.
Van Houten, B.; Kisker, C. Transcriptional pausing to scout ahead for DNA damage. Proc Natl Acad Sci USA. 2014, Mar 18; 111(11):3905-6. Doi: 10.1073/pnas.1402020111. Epub2014 Mar 5. PubMed PMID: 24599593; PubMed Central PMCID: PMC3964122.
Lan, L.; Nakajima, S.; Wei, L.; Sun, L.; Hsieh, C.L.; Sobol, R.W.; Bruchez, M.; Van Houten, B.; Yasui, A.; Levine, A.S. Novel method for site-specific induction of oxidative DNA damage reveals differences in recruitment of repair proteins to heterochromatin and euchromatin. Nucleic Acids Research. 2014, Feb 1;42(4):2330-45. PMCID:PMC3936713
Vaisman, A.; McDonald, J. P.; Huston, D.; Kuban, W.; Liu, L.; Van Houten, B.; Woodgate, R. Removal of misincorporated ribonucleotides from prokaryotic genomes: an unexpected role for nucleotide excision repair. PLoS Genetics. 2013, Nov 7; (11):e1003878. PMCID:PMC3820734
Hughes, C.; Wang, H.; Ghodke, H.; Simons, M.; Towheed, A.; Peng, Y.; Van Houten, B.; Kad, N. Real time single molecule imaging reveals a direct interaction between UvrC and UvrB on DNA tightropes. Nucleic Acids Res. 2013, March 19, May;41(9):4901-12. doi: 10.1093/nar/gkt177. Epub 2013 Mar 19. PMCID: PMC3643590.
Yeh, J.I.; Levine, A. S.; Du, S.; Chinte, U.; Ghodke, H.; Wang, H.; Shi, H; Hsieh, C. L.; Vu, T.; Conway, J. F.; Van Houten, B.; Rapić-Otrin, V. Damaged DNA induced UV-DDB dimerization and its roles on chromatinized DNA repair. Proc. Natl. Acad. Sci. 2012, 109(41):E2737-46 PMCID: PMC3478663.
Kad, N.M.; Wang, H.; Kennedy, G. G.; Warshaw, D.M.; Van Houten, B.; Collaborative dynamic DNA scanning by nucleotide excision repair proteins investigated by single-molecule fluorescence imaging of quantum dot labeled proteins. Molecular Cell. 2010, 37(5):702-13. PMID: 20227373
Wang, H.; Tessmer, I.; Croteau, D.L.; Erie, D.A.; Van Houten, B. Functional Characterization and Atomic Force Microscopy of a DNA Repair Protein Conjugated to a Quantum Dot. Nano Lett. 2008, Jun;8(6):1631-7.PMCID: PMC3941028