Proteins Involved in DNA Repair May Contribute to the Suppression of Cancer

Every day, cells in the body undergo numerous divisions. New cells are used to replace old, damaged or dead cells. However, before a cell divides, DNA is copied first to make a precise copy and passed on to the new cell.

To start the replication process, the DNA double helix unfolds first, so that each strand can be used as a template for the synthesis of new DNA. Scientists call the stretched DNA strand fragments replication forks. As this highly complex replication process proceeds, both strands of the original DNA may break or be damaged thousands of times.

"In fact, DNA sequences suffer considerable "damage" during replication, which is why complex mechanisms are needed to ensure that the replication process is protected." 

Accumulating evidence suggests that the pathway for repairing DNA breaks is called homologous recombination (HR). The key factor in HR is a protein called Rad51 that binds to a single DNA strand at the broken end and supports the replication fork by transforming the fork into a structure similar to a chicken foot.

In a recent study, the authors constructed mutants of RAD51 to better understand its key function at the replication fork. 

"We created a recombination-deficient variant of RAD51 that still binds DNA, but it does not search for complete copies of DNA or perform strand exchange," said the authors. "The more we learn about this process, the more likely we are to figure out how it creates problems in cancer, and we can help improve future treatment strategies."

In a recent study published in Nature Communications, Mason and his colleagues found that the strand-exchange activity of Rad51 is not required for the repair process, but that it is important to restart replication after removing the barrier.

"The field wants to understand the role of this pathway in cancer and the role of each participating factor," Mason said.

Other scientists in the field of cancer biology could apply the RAD51 gene mutation to their own studies to help further elucidate the replication process and better understand ways to repair breaks, Mason says.