A cell's ability to repair damage to its DNA is critical, and disrupting that repair function can lead to the development of cancer. New research carried out in the laboratory of Memorial Sloan-Kettering molecular biologist John H.J. Petrini has shed light on one mechanism that helps the cell respond to DNA damage and prevent it from being passed on when the cell divides to create new cells.

The study reveals that a complex of proteins called the MRE11 complex is able to suppress the formation of cancer in part by activating programmed cell death (apoptosis) when potentially cancer-causing DNA damage occurs. Earlier work by Dr. Petrini's lab showed that the MRE11 complex -- which is made up of the proteins MRE11, RAD50, and NBS1 -- helps ensure the integrity and stability of chromosomes and plays an important role in recognizing and repairing DNA damage. The complex was also known to function in the same DNA repair pathway as another protein called ATM kinase.

Using mouse models that lacked ATM and also had a mutant version of NBS1, the investigators induced DNA damage with ionizing radiation and studied cells' response to that damage both in the mice and in cell cultures. They were able to determine that the NBS1 component of the MRE11 complex controls apoptosis through its interaction with ATM and clarified that the MRE11 complex controls all of ATM's apoptotic functions.

"The MRE11 complex finds the site of the damage and invokes apoptosis much earlier in the process than previously thought," Dr. Petrini explained. "With the insight gained in this study, we now have a new potential target for coaxing cells to undergo apoptosis, which is enormously important in suppressing and treating cancer." The study was published in the May 10 issue of Nature. [PubMed Abstract]