With the unlikely but invaluable help of physicists, engineers and an electron accelerator, UW Medical School molecular biologists have found a way to examine how damaged genes are repaired in living cells.
The novel approach has enabled the Wisconsin team to definitively show what many scientists have long suspected but never been able to prove: within the seven-some-feet of the folded chromosome in every cell nucleus, special repair proteins do their work by moving immediately from their home bases to remote gene damage sites. The study is reported in the April 24 Science.
"In the past 24 hours, each chromosome in each cell of our bodies has been damaged by cancer-causing chemicals, ultraviolet radiation or free radicals, which are byproducts of several cellular processes," said UW Medical School assistant professor of medical genetics John Petrini. "But our cells are equipped with a system that constantly monitors and repairs the damaged DNA."
Petrini and his colleagues have focused their efforts on the system, a four-protein complex called MR95. In undamaged cells, MR95 also regulates DNA recombination, part of the cell-development cycle at the heart of heredity during which a chromosome that has split is rejoined to itself or another chromosome.
The UW researchers have been motivated by an intrinsic interest in this powerful, fundamental complex, which may also be essential to the development of reproductive cells, as well as the immune system. What's more, they hope their studies will provide a clearer picture of how chromosomes become unstable, a condition frequently associated with malignancy.
Petrini's team has made significant progress understanding the protein complex in studies of yeast, which offer a remarkably parallel model to the human DNA repair system. They've isolated genes associated with three of the four proteins, and produced mutant yeast and mice to study the way an inability to repair genes may lead to cancer.