Sir2 appears in organisms ranging from bacteria to mammals, suggesting that it plays a fundamental role in repression mechanisms. As is often the case, these new discoveries raise more questions than they answer. Jason Tanny, a graduate student in the Biological and Biomedical Sciences program, and Moazed and another group of researchers published two independent papers in the December Proceedings of the National Academy of Sciences Early Edition similarly giving the first detailed biochemical descriptions of Sir2's enzymatic activities, which show an intriguingly complicated reaction. In all eukaryotic organisms, DNA is packaged as chromatin, a condensed chain strung with nucleosome beads, which comprise about 146 base pairs of DNA coiled around a cluster of eight histone proteins. Proteins cannot get access to the DNA when it is clinging to the histones.
Access is mediated by the lysine-rich tails of the histones that stick out of the nucleosome.
Chemically speaking, transcription, repair, and recombination can only begin when an acetyl group attaches to the lysine side chains and neutralizes the positive charge on the histone tails. In the silent chromatin of yeast, histone protein tails remain relatively free of acetyl groups compared to the rest of the genome. Scientists have seen similar hypoacetylation in the silent chromatin of fruit flies and mammals, notably the chromatin regions around centromeres and along the inactive X chromosome in female mammals. Sir2's role, however, remained a mystery. About two years ago came the first indirect evidence from studies of a similar protein involved in a vitamin B12 biosynthesis pathway in a bacterium.