UC Davis scientists have determined a protein vital in repairing breaks in copied DNA. This important discovery builds pathways to understanding more about cells resistance toward radiation and chemotherapy.
Genetic recombination allows for cells to ensure accurate chromosome segregation and in turn essential for genomic stability and tumor suppression.
The protein, called proliferating cell nuclear antigen (PCNA), forms a ring around DNA so that it remains in place and may attach to DNA polymerase. The study says that PCNA endows DNA polymerases with high processivity. The key effect PCNA has is to function during recombination – when cells divide to form eggs and sperm – in addition to trying to repair breaks across the double-strand helix.
“Genetic studies and recent clinical studies show that cells lacking or blocked in recombinational DNA repair become very sensitive to anti-cancer drugs that act by affecting DNA replication or by introducing DNA breaks,” said Stephen Kowalczykowski, distinguished professor in microbiology at UC Davis in an e-mail interview.
The importance of killing cancer cells lies in one key factor said Wolf-Dietrich Heyer, professor of microbiology at UC Davis and leader of the molecular oncology program at the UC Davis Cancer Center.
“Cancer cells are actively dividing while most other cells aren’t,” Heyer said. “Radiation can exploit the cell.”
Cells become cancerous primarily through mutations and genetic
predispositions whereas normal cells retain genome integrity. If a cell is irradiated, significant damage occurs.
Cells have two methods of dealing with radiation: They either repair and survive, through the repair reaction, or they go through apoptosis (programmed cell death).
“Cancer cells have lost the ability to do apoptosis so they need to rely on DNA repair to stay indefinitely alive,” Heyer said.
Understanding the repair reaction and how DNA recombination works is vital to dealing with cancer tumors, Heyer said.
The repair reaction assists in binding PCNA to polymerase more efficiently, in turn holding cancerous cells in place. Holding these cells in place can significantly increase cancer treatment.
“Most anti-cancer drugs kill cancerous cells by damaging their DNA, cancer cells grow and replicate their DNA rapidly, and in a relatively uncontrolled manner; hence, tumors are more sensitive to DNA-damaging agents than normal cells,” Kowalczykowski said.
An example of a gene involved in DNA repair is BRCA-2, which induces breast and ovarian cancer.
If problems exist with this gene the likelihood of being diagnosed with cancer is almost 100 percent, Heyer said.
He added that the most promising benefit of this discovery is that it’s among the first to identify how DNA functions in the repair reaction and synthesizing DNA. It also gives insight into the molecules utilized and how they function when exposed to carcinogens, or cancer-causing agents.
“The application of this discovery is down the road but it’s promising,” Heyer said.
SADAF MOGHIMI can be reached at firstname.lastname@example.org.