Genome-wide Analysis of DNA Damage Formation and Repair
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.
1. 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/
2. 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).
3. Mao, P. and Wyrick, J. J. (2016) Emerging Roles for Histone Modifications in DNA Excision Repair. FEMS Yeast Research (in press).
4. 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.
5. 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.
6. 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.
7. Wyrick, J. J. and Roberts, S. A. (2015) Genomic approaches to DNA repair and mutagenesis. DNA repair 36:146-155.