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Harvard Medical School

  December 17, 2004

yang shiGENETICS: Protein Reverses Chromatin Engineering
Researchers have discovered an enzyme that plays an important role in controlling which genes will be turned on or off at any given time in a cell. The elusive enzyme, whose presence in cells was suspected for decades but not proven, came to light for the first time in the laboratory of Yang Shi. The findings appear in Cell online and in the Dec. 29 print edition. The enzyme, a histone demethylase, removes methyl groups appended to histone proteins that associate with DNA to form the nuclear chromatin structure and regulate gene activity. The molecule could potentially reverse over-methylation of some histones, which leads to aberrant gene expression and cancer.

stephen buratowskiBIOLOGICAL CHEMISTRY: Molecule Implicated in Transcription Termination
Termination of transcription, the synthesis of messenger RNA from DNA, has puzzled scientists for years. Unlike the translation of RNA into protein, which ends once ribosomes hit stop codons, there are no stop signals for the transcriptional enzyme RNA polymerase II. In the Nov. 25 Nature, Stephen Buratowski and colleagues show that transcription termination in yeast occurs after recruitment of several proteins, including the ribonuclease Rat1, to the C-terminal domain of the RNA polymerase. This happens after the finishing steps in mRNA synthesis have cut the nucleic acid, exposing the uncapped (and therefore unprotected) head of a trailing RNA strand. Termination occurs, according to the model, because Rat1, which can digest the leftover RNA faster than it is being made, catches up to the catalytic domain of the polymerase, at which point the entire complex separates from the DNA, ceasing transcription.

John Pascal (left), Tom EllenbergerSTRUCTURAL BIOLOGY: DNA Splicing Enzyme Observed in Action
Somehow, people have trillions of perfect copies of their original chromosomes, one set for each cell. Now, researchers have discovered the shape of the molecule that puts the final touches on replicating chromosomes in dividing cells by patching together loose ends of DNA. The enzyme looks like a doughnut, report John Pascal (left), Tom Ellenberger, and colleagues in the Nov. 25 Nature. The paper represents the first X-ray crystal structure of a ligase bound to DNA.

Copyright 2004 by the President and Fellows of Harvard College