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The official name of this gene is “nibrin.”
NBN is the gene's official symbol. The NBN gene is also known by other names, listed below.
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 MRE11A and RAD50 genes, as part of a larger protein complex. Nibrin regulates the activity of this complex by carrying the MRE11A and RAD50 proteins into the cell's nucleus and guiding them to sites of DNA damage. The proteins work together to mend broken strands of DNA. 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. Repairing DNA prevents cells from accumulating genetic damage that may cause them to die or to divide uncontrollably.
The MRE11A/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. The MRE11A/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.
At least 10 mutations in the NBN gene have been found to cause Nijmegen breakage syndrome, a condition characterized by slow growth, recurrent infections, and an increased risk of developing cancer. The NBN gene mutations that cause Nijmegen breakage syndrome typically lead to the production of an abnormally short version of the nibrin protein. The mutation found in most affected individuals, particularly in Slavic populations of Eastern Europe, deletes five DNA building blocks (nucleotides) from the NBN gene (written as 657_661del5). This mutation leads to the production of a shortened version of the nibrin protein called p70-nibrin. This shortened protein is not as effective as normal nibrin in responding to DNA damage, but p70-nibrin does appear to have some residual function.
When breaks in DNA are not repaired properly, genetic damage can accumulate. A buildup of mistakes in DNA can trigger cells to grow and divide abnormally, increasing the risk of cancer in people with Nijmegen breakage syndrome. Nibrin's role in regulating cell division and cell growth (proliferation) is thought to lead to the problems with the immune system that are seen in affected individuals. A lack of functional nibrin results in less immune cell proliferation. A decrease in the amount of immune cells that are produced leads to a malfunctioning immune system. It is unclear how mutations in the NBN gene cause the other features of Nijmegen breakage syndrome.
Recent studies suggest that certain inherited changes in the NBN gene may be associated with an increased risk of developing breast cancer. The c.657_661del5 mutation that is commonly seen in people with Nijmegen breakage syndrome is thought to increase the risk of breast cancer in people who have one copy of the mutation in each cell. It is estimated that people who have the c.657_661del5 mutation have a threefold increased risk of developing breast cancer compared to individuals who do not have this mutation. A few other mutations in the NBN gene have also been associated with an increased risk of developing breast cancer. Researchers believe that the NBN gene mutations associated with breast cancer prevent nibrin from responding effectively to DNA damage. As defects accumulate in DNA, they can trigger cells to grow and divide uncontrollably, causing cancer.
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 in each cell 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. Cells with a mutation in one copy of the NBN gene do not repair DNA as effectively as cells without these mutations. It is thought that DNA damage accumulates over time, which can trigger cells to grow and divide uncontrollably and increase the risk of developing cancer.
Cytogenetic Location: 8q21
Molecular Location on chromosome 8: base pairs 90,945,563 to 90,996,951
The NBN gene is located on the long (q) arm of chromosome 8 at position 21.
More precisely, the NBN gene is located from base pair 90,945,563 to base pair 90,996,951 on chromosome 8.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about NBN helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
cancer ; cell ; cell cycle ; cell division ; cell proliferation ; DNA ; DNA damage ; gene ; immune system ; leukemia ; melanoma ; mutation ; nucleus ; ovarian ; proliferation ; prostate ; protein ; radiation ; syndrome ; telomere ; toxic ; tumor
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.