Enzymes that protect the integrity of the genome

Enzymes that protect the integrity of the genomeDNA is startlingly prone to chemical damage, by both exogenous and endogenous species. Such damage is associated with mutagenesis, carcinogenesis and aging. Repair of DNA is initiated by a family of enzymes called glycosylases.

In two recent papers, Professor Jeehiun K. Lee and her group at CCB use a combination of experimental and theoretical methods to characterize both natural and artificial substrates of two glycosylases, AlkA and MutY. These studies lend unique insight into the mechanism of these two genome-protecting enzymes.

Image from the RCSB PDB (http://www.rcsb.org/pdb/home/home.do) of PDB ID 3FSQ (O'Shea, V.L., Cao, S., Richards, J.L., Horvath, M.P., David, S.S. Structural illumination of a mutY glycosylase reaction coordinate intermediate; DOI:10.2210/pdb3fsq/pdb)


These papers were featured in the Journal of the American Chemical Society in 2012:

Michelson, A. Z.; Rozenberg A.; Tian, Y.; Sun, X., Davis, J.; Francis, A. W.; O’Shea, V., Halasyam, M.; Manlove, A. H.; David, S.; Lee, J. K. Gas Phase Studies of Substrates for the DNA Mismatch Repair Enzyme MutY. J. Am. Chem. Soc. 2012, 134, 19839-19850 (DOI: 10.1021/ja309082k)

Michelson, A. Z.; Chen, M.; Wang, K.; Lee, J. K. Gas Phase Studies of Purine 3-Methyladenine DNA Glycosylase II (AlkA) Substrates. J. Am. Chem. Soc. 2012, 134, 9622–9633 (DOI: 10.1021/ja211960r)

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