ST. LOUIS — In a new paper published in Nature Communications, a team led by Saint Louis University researcher Alessandro Vindigni, Ph.D. shares new information about how BRCA-deficient cancer cells operate, interact with chemotherapy drugs and what may be their last-ditch effort to survive. Researchers hope their findings may lead to improved chemotherapy drugs and shed light on why some cells develop chemotherapy resistance.
Vindigni, who is professor of biochemistry and molecular biology at SLU, studies genome integrity, the ability of a cell to faithfully transmit its DNA information on to new cells.
As cells create duplicate copies of their genetic material, a lesion or other obstacle can block DNA replication, potentially derailing a cell’s ability to reproduce. Lesions in DNA can occur as often as 100,000 times per cell per day. They can be the result of normal metabolic activities, like free radicals, as well as exposure to environmental factors such as UV radiation, X-rays and chemical compounds. If a cell’s replication machinery collides with the lesion, a strand break can occur.
When confronted with a lesion, cells have repair strategies, including a tactic called fork reversal. DNA replicates by unzipping its two interwoven strands and making copies of each. As the DNA strands separate and copy, they form a “replication fork.” If these forks run into obstacles like lesions that block their progress, cells perform a maneuver called fork reversal