Dr. John J. Wyrick
Research & Interests
We are investigating how DNA damage is formed and repaired in chromatin on a genome-wide scale, and how damage formation and repair influences subsequent mutagenesis. Our focus has been on UV-induced DNA damage, which is primarily repaired by nucleotide excision repair (NER) pathway. We are also investigating how nucleosome positioning and histone modifications regulate the repair of DNA base lesions throughout the genome. To advance these studies, we have developed novel genomic tools to map DNA lesions at single-nucleotide resolution throughout the yeast and human genomes. We have also been investigating how chromatin impacts CRISPR-Cas9 genome editing.
Chromatin and DNA repair
Kong, M., Liu, L., Chen, X., Driscoll, K.I., Mao, P., Bohm, S., Kad, N.M., Watkins, S.C., Bernstein, K.A., Wyrick, J.J., Min, J.H., and Van Houten, B. (2016) Single-molecule imaging reveals that Rad4 (XPC) employs a dynamic DNA damage recognition process. Molecular Cell, DOI: http://dx.doi.org/10.1016/j.molcel.2016.09.005/
Mao, P., Wyrick, J.J., Roberts, S.A., and Smerdon, M.J. (2016) UV-Induced DNA Damage and Mutagenesis in Chromatin. Photochem Photobiol. (in press).
Mao, P. and Wyrick, J. J. (2016) Emerging Roles for Histone Modifications in DNA Excision Repair. FEMS Yeast Research (in press).
Mao, P., Smerdon, M.J., Roberts, S.A., and Wyrick, J.J. (2016) Chromosomal landscape of UV damage formation and repair at single-nucleotide resolution. Proc Natl Acad Sci USA 113:9057-9062.
Mao, P., Kyriss, M. N. M., Hodges, A. J., Duan, M., Morris, R. T., Lavine, M. D., Topping, T. B., Gloss, L. M., and Wyrick, J. J. (2016) A Basic Domain in the Histone H2B N-terminal Tail is Important for Nucleosome Assembly by FACT. Nucleic Acids Res., published online Jul 1. pii: gkw588.
Rodriguez, Y., Hinz, J. M., Laughery, M. F., Wyrick, J. J., and Smerdon, M. J. (2016) Site-specific Acetylation of Histone H3 Decreases Polymerase Î² Activity on Nucleosome Core Particles in vitro. J. Biol. Chem. 291:11434-11445.
Wyrick, J. J. and Roberts, S. A. (2015) Genomic approaches to DNA repair and mutagenesis. DNA repair 36:146-155.
Meas, R., Smerdon, M. J. & Wyrick, J. J. (2015) The amino-terminal tails of histones H2A and H3 coordinate efficient base excision repair, DNA damage signaling and postreplication repair in Saccharomyces cerevisiae. Nucleic Acids Res. 43:4990-5001.
Hodges, A. J., Gallegos, I. J., Laughery, M. F., Meas, R., Tran, L. & Wyrick, J. J. Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability in Saccharomyces cerevisiae. Genetics 200, 795-806, (2015). PMCID: PMC4512544.
Zavala, A. G., Morris, R. T., Wyrick, J. J. and Smerdon, M. J. (2014) High Resolution Characterization of CPD Hotspot Formation in Human Fibroblasts, Nucleic Acids Res. 42: 893-905.
Wyrick, J. J., Kyriss, M. N., and Davis, W. B. (2012) Ascending the nucleosome face: recognition and function of structured domains in the histone H2A-H2B dimer. Biochim Biophys Acta 1819:892-901.
Kyriss, M.N., Jin, Y., Gallegos, I.J., Sanford, J.A., and Wyrick, J.J. (2010) Novel functional residues in the core domain of histone H2B regulate yeast gene expression and silencing and affect the response to DNA damage. Mol. Cell. Biol. 30:3503-3518.
Zheng, S., Wyrick, J.J., Reese, J.C. (2010) Novel trans-tail regulation of H2B ubiquitylation and H3K4 methylation by the N-terminus of histone H2A. Mol Cell Biol. 30:3635-45.
Nag, R., Kyriss, M., Smerdon, J.W., Wyrick, J.J., Smerdon, M.J. (2010) A cassette of N-terminal amino acids of histone H2B are required for efficient cell survival, DNA repair and Swi/Snf binding in UV irradiated yeast. Nucleic Acids Res. 38:1450-1460.
Jin, Y., Rodriguez, A.M., Wyrick, J.J. (2009) Genetic and Genome-wide Analysis of Simultaneous Mutations in Acetylated and Methylated Lysine Residues in Histone H3 in Saccharomyces cerevisiae. Genetics 181:461-472.
Chaudhuri, S., Wyrick, J.J., Smerdon, M.J. (2009) Histone H3 Lys79 Methylation is Required for Efficient Nucleotide Excision Repair in a Silenced Locus of Saccharomyces cerevisiae. Nucleic Acids Res. 37:1690-1700.
Wyrick, J.J. and Parra, M.A. (2009) The role of histone H2A and H2B post-translational modifications in transcription: A genomic perspective. Biochim Biophys Acta. 1789:37-44.
Parra, M.A. and Wyrick, J.J. (2007) Regulation of gene transcription by the histone H2A N-terminal domain. Mol. Cell. Biol. 27:7641-7648.
Jin, Y., Rodriguez, A.M., Stanton, J.D., Kitazono, A.A., and Wyrick, J.J. (2007) Simultaneous mutation of methylated lysine residues in histone H3 causes enhanced gene silencing, cell cycle defects, and cell lethality in S. cerevisiae. Mol. Cell. Biol. 27:6832-6841.
Wood, A., Shukla, A., Schneider, J., Lee, J.S., Stanton, J.D., Dzuiba, T., Swanson, S.K., Florens, L., Washburn, M.P., Wyrick, J., Bhaumik, S.R., Shilatifard, A (2006) Ctk complex mediated regulation of histone methylation by COMPASS. Mol Cell Biol 27:709-720.
Parra, M.A., Kerr, D., Fahy, D., Pouchnik, D.J., and Wyrick, J.J. (2006) Deciphering the Roles of the Histone H2B N-terminal domain in Genome-wide Transcription. Mol Cell Biol 26:3842-3852.
Martin, A.M., Pouchnik, D.J., Walker, J.L., and Wyrick, J.J. (2004) Redundant Roles for Histone H3 N-Terminal Lysine Residues in Subtelomeric Gene Repression in Saccharomyces cerevisiae. Genetics 167:1123-1132.
Lee, T.I., Rinaldi, N.J., Robert, F., Odom, D.T., Bar-Joseph, Z., Gerger, G.K., Hannett, N.M., Harbison, C.T., Thompson, C.M., Simon, I., Zeitlinger, J., Jennings, E.G., Murray, H.L., Gordon, D.B., Ren, B., Wyrick, J.J., Tagne, J.B., Volkert, T.L., Fraenkel, E., Gifford, D.K., Young, R.A. (2002) Transcriptional Regulatory Networks in Saccharomyces cerevisiae. Science 298: 799-804.
Wyrick, J.J. and Young, R.A. (2002) Deciphering Gene Expression Regulatory Networks. Curr Opin Genet Dev 12: 130-6.
Wyrick, J.J.*, Aparicio, J.G.*, Chen, T., Barnett, J.D., Jennings, E.G., Young, R.A., Bell, S.P., and Aparicio, O.M. (2001) Genome-Wide Distribution of ORC and MCM proteins in S. cerevisiae: High-Resolution Mapping of Replication Origins. Science 294: 2357-2360. *Authors made equal contributions.
Simon, I., Barnett, J., Hannett, N., Harbison, C.T., Rinaldi, N.J., Volkert, T.L., Wyrick, J.J., Zeitlinger, J., Gifford, D.K., Jaakkola, T.S., and Young, R.A. (2001) Serial Regulation of Transcriptional Regulators in the Yeast Cell Cycle. Cell 106: 697-708.
Ren, B.*, Robert, F.*, Wyrick, J.J.*, Aparicio, O., Jennings, E.J., Simon, I., Zeitlinger, J., Schreiber, J., Hannett, N., Kanin, E., Volkert, T.L., Wilson, C.J., Bell, S.P., and Young, R.A. (2000) Genome-wide Location and Function of DNA-binding Proteins. Science 290: 2306-2309. *Authors made equal contributions.
Wyrick, J.J., Holstege, F.C.P., Jennings, E.G., Causton, H.C., Shore, D., Grunstein, M., Lander, E.S., Young, R.A., (1999) Chromosomal Landscape of Nucleosome-dependent Gene Expression and Silencing in Yeast. Nature 402:418-421.
Holstege, F.C.P., Jennings, E.G., Wyrick, J.J., Lee T., Hengartner, C.J., Green, M.R., Golub, T.R., Lander, E.S., and Young, R.A. (1998) Dissecting the Regulatory Circuitry of a Eukaryotic Genome. Cell 95: 717-728.
Lee, T., Wyrick, J.J., Koh, S.S., Jennings, E.G., Gadbois, E.L., and Young, R.A. (1998) Interplay of Positive and Negative Regulators in Transcription Initiation by RNA Polymerase II Holoenzyme. Mol. Cell. Biol. 18: 4455-4462.
Plant and Yeast Bioinformatics
Morris, R.T., Doroshenk, K.A., Crofts, A.J., Lewis, N., Okita, T.W., Wyrick, J.J. (2011) RiceRBP: A database of experimentally identified RNA-binding proteins in Oryza sativa L. Plant Science 180:204-11.
Doroshenk, K.A., Crofts A.J., Washida, H., Satoh-Cruz, M., Crofts, N., Sugino, A., Okita, T.W., Morris, R.T., Wyrick, J.J., Fukuda, M., Kumamaru, T., and Satoh, H. (2010) Characterization of the rice glup4 mutant suggests a role for the small GTPase Rab5 in the biosynthesis of carbon and nitrogen storage reserves in developing endosperm. Breeding Science 60:556-567.
Morris, R.T., O'Connor, T.R., and Wyrick, J.J. (2010) Ceres: software for the integrated analysis of transcription factor binding sites and nucleosome positions in Saccharomyces cerevisiae. Bioinformatics 26:168-174.
Doroshenk, K.A., Crofts, A.J., Morris, R.T., Wyrick, J.J., Okita, T.W. (2009) Proteomic analysis of cytoskeleton-associated RNA binding proteins in developing rice seed. J Proteome Res. 8:4641-4653.
Morris, R.T., O'Connor, T.R., and Wyrick, J.J. (2008) Osiris: an integrated promoter database for Oryza sativa L. Bioinformatics 24:2915-2917.
O'Connor, T.R. and Wyrick, J.J. (2007) ChromatinDB: a database of genome-wide histone modification patterns for Saccharomyces cerevisiae. Bioinformatics (in press).
O'Connor, T.R., Dyreson, C., and Wyrick, J.J. (2005) Athena: a resource for rapid visualization and systematic analysis of Arabidopsis promoter sequences. Bioinformatics 21:4411-4413.
Wyrick, J.J., Young, R.A., Ren, B., and Robert, F. "Chromosome-wide analysis of protein-DNA interactions," US patent# 6,410,243; June 25, 2002.
Wyrick, J., Young, R.A., Ren, B., Robert, F., Simon, I. "Genome-wide location and function of DNA binding proteins," US 7,470,507; December 30, 2008.
Wyrick, J., Young, R.A., Ren, B., Robert, F., Simon, I. "Genome wide location and function of DNA binding proteins," US 7,575,869; August 18, 2009.