(SACRAMENTO, Calif.) An international team of scientists led by UC Davis researchers has discovered that DNA repair in cancer cells is not a one-way street as previously believed. Their findings show instead that recombination, an important DNA repair process, has a self-correcting mechanism that allows DNA to make a virtual u-turn and start over.
The study's findings, which appear in the Oct. 23 online issue of the journal Nature, not only contribute new understanding to the field of basic cancer biology, but also have important implications for potentially improving the efficacy of cancer treatments.
"What we discovered is that the DNA repair pathway called recombination is able to reverse itself," said Wolf-Dietrich Heyer, UC Davis professor of microbiology and of molecular and cellular biology and co-leader of Molecular Oncology at UC Davis Cancer Center. "That makes it a very robust process, allowing cancer cells to deal with DNA damage in many different ways. This repair mechanism may have something to do with why some cancer cells become resistant to radiation and chemotherapy treatments that work by inducing DNA damage."
Heyer likens this self-correcting ability of the DNA repair system to driving in a modern city where u-turns and two-way streets make it easy to rectify a wrong turn. "How much harder would it be to re-trace your path if you were in a medieval Italian city with only one-way streets," he said.
In the current study, Heyer and his colleagues used yeast as a model system to elucidate the mechanisms of DNA repair. They expect their findings, like most that come out of work on yeast, will be confirmed in humans. "Whether in yeast or humans, the pathways that repair DNA are the same," Heyer said.
The research team used electron microscopy to observe repair proteins in action on strands of DNA. They saw a presynaptic filament called Rad51 regulating the balance between one enzyme (Rad55-Rad
|Contact: Dorsey Griffith|
University of California - Davis Health System