Abstract
Genomes undergo massive amounts of modifications, both in the DNA and the associated proteins. A large number of enzymes catalyze these modifications. This chapter focuses on the chemistry behind a myriad of modifications that occur on the genome. The diversity of both the chemical mechanisms and the enzymes that catalyze the chemical reactions are breathtaking.•In the first section, we have reviewed the principles behind chemical reactions that occur in the genome. Some readers may find this redundant, but this section aims to refresh the memory of the readers who do not deal with chemistry on a day-to-day basis. We have described the electronic structures and properties of amino acid side chains of proteins and bases present in the DNA. We have reviewed some basic concepts of chemical equilibrium and kinetics. We have briefly described some aspects of enzyme catalysis that we have used in the following sections.•In the second section, we have described mechanisms of common types of reactions that occur on the genome. The major ones are the nucleophilic substitutions and additions,β-elimination, and free-radical reactions.•In the third section, we have discussed the reactions that modify the DNA. Some of these are enzymatic modifications, but some others are reactions that occur without the involvement of enzymes. The most prominent reactions discussed are methylation and demethylation of the DNA bases, strand breaks, deamination of cytosine, and repair of modified bases.•In the fourth section, we have discussed chemical modifications of proteins and enzymes that catalyze such modifications. Major chemical modifications that were covered include phosphorylation, acetylation, ADP-ribosylation, and methylation of lysines and arginines. We have also discussed the oxidation of cysteine and redox regulation of enzyme activities. For each modification, we have discussed the chemical mechanisms and the enzymes that catalyze such modifications. In each case, we have also discussed the reverse reactions and enzymes that catalyze the reverse reaction.