DNA repair, mutagenesis, cancer, and Cas9 genome editing
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.
Research PublicationsChoi, J.A. and Wyrick, J.J. (2017) RegulatorDB: a resource for the analysis of yeast transcriptional regulation. Database (Oxford). doi: 10.1093/database/bax058.
Mao, P., Brown, A.J., Malc, E.P., Mieczkowski, P.A., Smerdon, M.J., Roberts, S.A., and Wyrick, J.J. (2017) Genome-wide maps of alkylation damage, repair, and mutagenesis in yeast reveal mechanisms of mutational heterogeneity. Genome Res. 27:1674-1684.
Hodges, A.J., Gloss, L.M., and Wyrick, J.J. (2017) Residues in the Nucleosome Acidic Patch Regulate Histone Occupancy and Are Important for FACT Binding in Saccharomyces cerevisiae. Genetics 206:1339-1348.
Mao, P., Wyrick, J.J., Roberts, S.A., and Smerdon, M.J. (2017) UV-Induced DNA Damage and Mutagenesis in Chromatin. Photochem. Photobiol., 93:216-228.
Hinz, J.M., Laughery, M.F., and Wyrick, J.J. (2016) Nucleosomes Selectively Inhibit Cas9 Off-Target Activity at a Site Located at the Nucleosome Edge. J Biol Chem. 291:24851-24856.
Kong, M., Liu, L., Chen, X., Driscoll, K.I., Mao, P., Böhm, 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 64:376-387.
Rodriguez, Y., Hinz, J.M., Laughery, M.F., Wyrick, J.J., and Smerdon, M.J. (2016) Site-specific Acetylation of Histone H3 Decreases Polymerase β Activity on Nucleosome Core Particles in vitro. J. Biol. Chem. 291:11434-11445.
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. 44:9142-9152.
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.
Hinz, J.M., Laughery, M.F. and Wyrick, J.J. (2015) Nucleosomes Inhibit Cas9 Endonuclease Activity in Vitro. Biochemistry, 54:7063-7066.