Brona McVittie reports :: October 2006

Evidently inspired by his dad, Arthur Kornberg, who won the Nobel prize in 1959 for his work on describing the DNA polymerase enzyme that facilitates DNA replication, young Roger published a research paper in 2001 that set the scientific community abuzz. Using X-ray crystallography, as was used to unravel the crystal structure of DNA, Kornberg’s team created an intricately detailed architectural model of the enzyme.

Furthermore they caught RNA polymerase II in the act, as it were, of making RNA from DNA. Equipped with clamp, saddle, zipper, rudder, lid, linker, funnel and jaws, the masterful enzyme admits the DNA double-helix into a groove near the active site, via its jaws. DNA strands unwind, allowing RNA nucleotides, through a tiny pore, to line up along the DNA. The newly formed RNA molecules jut out at right angles before breaking away in search of ribosomes, where they instruct protein manufacture.

Although many researchers had a fair idea of transcription, mainly by inference, no one had ever before described the process in such detail with the crystallographic evidence. In fact, RNA polymerase II is part of a complex series of events that are necessary to tease DNA away from nucleosomes, little histone bundles also described (at least in part) by Kornberg. These basic units of chromatin (seen as beads on a string in the picture above) are common to most cells with a nucleus i.e. not bacteria, and are instrumental in gene regulation.

Around 150 base-pairs of DNA encircle every histone bundle (nucleosome). While this keeps the nucleus tidy, it doesn’t help transcription, when DNA has to peel away from protein bundles to allow RNA polymerase II to make RNA. As Thomas Jenuwein (Institute of Molecular Pathology, Vienna) notes, “While DNA is the unit for genetic information, the nucleosome is the unit of epigenetic information that can respond to environmental signals and influence the way genes work. Roger Kornberg and other scientists have described the basic principles for the conversion of stored (DNA) to functional (RNA) information in eukaryotic chromatin.”