NBN

The NBN gene provides instructions for making a protein called nibrin. This protein is involved in several critical cellular functions, including the repair of damaged DNA.

Nibrin interacts with two other proteins, produced from the MRE11 and RAD50 genes, as part of a larger protein complex. Nibrin regulates the activity of this complex by carrying the MRE11 and RAD50 proteins into the nucleus and guiding them to sites of DNA damage. The proteins work together to mend broken strands of DNA, which prevents cells from accumulating genetic damage that can trigger them to divide uncontrollably.

The MRE11/RAD50/NBN complex interacts with the protein produced from the ATM gene, which plays an essential role in recognizing broken strands of DNA and coordinating their repair. DNA can be damaged by agents such as toxic chemicals or radiation, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material in preparation for cell division.

The MRE/RAD50/NBN complex helps maintain the stability of a cell's genetic information through its roles in repairing damaged DNA and regulating cell division. Because these functions are critical for preventing the formation of cancerous tumors, nibrin is described as a tumor suppressor.

breast cancer - associated with the NBN gene

Recent studies suggest that certain inherited changes in the NBN gene may be associated with an increased risk of developing breast cancer, particularly in Slavic populations of Eastern Europe. Researchers believe that these mutations prevent nibrin from responding effectively to DNA damage. As defects accumulate in DNA, they can trigger cells to grow and divide uncontrollably and form a tumor.

other disorders - caused by mutations in the NBN gene

At least eight mutations in the NBN gene have been identified in people with a condition called Nijmegen breakage syndrome (NBS). This condition results when a person is born with two altered copies of the NBN gene in each cell. Nijmegen breakage syndrome is characterized by slow growth and short stature, an abnormally small head size (microcephaly), mild to moderate intellectual disability, distinctive facial features such as a sloping forehead and prominent nose, and recurrent respiratory infections. About 50 percent of people with this condition also develop cancer, most commonly a cancer of immune system cells (lymphoma).

Each of the mutations that cause this condition leads to the production of an abnormally short version of the nibrin protein. The defective protein is missing important regions, preventing it from responding to DNA damage effectively. As a result, breaks in DNA are not repaired properly and genetic damage can accumulate. This buildup of mistakes in DNA can trigger cells to grow and divide abnormally, increasing the risk of cancer in people with Nijmegen breakage syndrome.

other cancers - associated with the NBN gene

Inherited mutations in the NBN gene have also been associated with several other types of cancer. Studies in Eastern European populations reported that people with mutations in one copy of the NBN gene may be more likely to develop prostate cancer, ovarian cancer, an aggressive form of skin cancer (melanoma), or cancer of blood-forming cells (leukemia) than people who do not carry NBN mutations. Research is under way to investigate whether changes in the NBN gene contribute to a person's overall risk of developing cancer.