BRCA1

Overview
BRCA1 (breast cancer 1, early onset) is a human gene that belongs to a class of genes known as tumor suppressors, which regulate the cell cycle and prevent uncontrolled proliferation. The BRCA1 protein product of the gene is part of the DNA damage detection and repair system. Variation in the gene has been implicated in some cancers. The BRCA1 gene is located on the long (q) arm of chromosome 17 at position 21, from base pair 38,449,843 to base pair 38,530,933.

Function and mechanism
The BRCA1 protein is directly involved in the repair of damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein is thought to interact with RAD51 to mend breaks in DNA, though the details and significance of this interaction is the subject of debate. These breaks can be caused by natural radiation or other exposures, but also occur when chromosomes exchange genetic material in preparation for cell division. The BRCA2 protein, which has a function similar to that of BRCA1, also interacts with the RAD51 protein. By repairing DNA, these three proteins play a role in maintaining the stability of the human genome.

Research suggests that both the BRCA1 and BRCA2 proteins regulate the activity of other genes and play a critical role in embryo development. The BRCA1 protein probably interacts with many other proteins, including tumor suppressors and regulators of the cell division cycle.

Mutations
Certain variations of the BRCA1 gene lead to an increased risk for breast cancer. Researchers have identified more than 600 mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer.

These mutations can be changes in one or a small number of DNA base pairs (the building blocks of DNA). Those mutations can be looked for using PCR and sequencing.

In some cases, large segments of DNA are rearranged. Those large segments, called also large rearrangements, can be a deletion or a duplication of one or several exons in the gene. Classical methods for mutations detection(sequencing) are unable to reveal those mutations. . Other methods are proposed : Q-PCR, Multiplex Ligation-dependent Probe Amplification (MLPA) , and Quantitative Multiplex PCR of Shorts Fluorescents Fragments (QMPSF). New methods have been recently proposed : heteroduplex analysis (HDA) by multi-capillary electrophoresis or also dedicated oligonucleotides array based on comparative genomic hybridization (array-CGH).

A mutated BRCA1 gene usually makes a protein that does not function properly because it is abnormally short. Researchers believe that the defective BRCA1 protein is unable to help fix mutations that occur in other genes. These defects accumulate and may allow cells to grow and divide uncontrollably to form a tumor.

In addition to breast cancer, mutations in the BRCA1 gene also increase the risk on ovarian, Fallopian tube, prostate and colon cancers. Moreover, precancerous lesions (dysplasia) within the Fallopian tube have been linked to BRCA1 gene mutations.