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Discovering the first steps in transcription-coupled repair

A team of scientists led by Priscilla Cooper, a senior staff scientist in the Life Sciences Division of the Department of Energy's Lawrence Berkeley National Laboratory, has discovered new players in the first steps of transcription-coupled repair (TCR), an essential but still mysterious mechanism of DNA repair.

If a blockage occurs when genetic information from a cell's DNA is being transcribed into RNA -- an activity vital to the synthesis of proteins -- the transcription-coupled repair (TCR) process detects the obstruction and repairs the damage. But when TCR itself fails, the results can be lethal to cells and to the organism. In humans, failure of transcription-coupled repair is the cause of Cockayne Syndrome, an extreme form of accelerated aging that is inevitably fatal early in life.

Cooper and her colleagues illuminated, for the first time, the roles played by two important proteins in recognizing blockages in transcription and in initiating an efficient method of repair; their results suggested a previously unsuspected mechanism for the repair process.

The team, whose members hold positions at Berkeley Lab, the University of California at Berkeley, the Howard Hughes Medical Institute, the Skaggs Institute for Chemical Biology, and the Scripps Research Institute, includes Altaf Sarker, Susan Tsutakawa, Seth Kostek, Cliff Ng, David Shin, Marian Peris, Eric Campeau, John Tainer, and Eva Nogales, in addition to Cooper. Their results appear in the October 28, 2005 issue of the journal Molecular Cell.

DNA repair: keeping up with life

DNA is constantly under attack from sources inside and outside the body, including sunlight, ionizing radiation, other environmental carcinogens, and free radicals from the cellular metabolism. DNA damage ranges from one or a few altered nucleotides in a single strand of the double helix, to breaks in one or both strands and crosslinks between the two strands. To prevent accumulation of m
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Source:DOE/Lawrence Berkeley National Laboratory


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