What is the Function of the BRCA Gene?

The human body contains genes that provide instructions for making proteins. Two of these, BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2), produce proteins that function as caretakers of our genetic material. Everyone has two copies of each gene, one inherited from each parent. These genes and the proteins they encode are part of a system that maintains the stability of a cell’s DNA, which is a component of normal cellular health.

BRCA as a Tumor Suppressor

The BRCA genes belong to a class known as tumor suppressor genes. These genes act as a braking system for cell growth, ensuring that cells do not multiply in an uncontrolled manner. The proteins produced by BRCA1 and BRCA2 are found in the nucleus of cells and are directly involved in DNA repair. They are part of a large protein complex that constantly surveils the genome for damage.

One of their most understood functions is repairing a specific type of DNA damage called double-strand breaks. These breaks can be caused by environmental exposures like radiation or as a byproduct of normal cellular processes. The BRCA proteins orchestrate a high-fidelity repair process known as homologous recombination. This process uses the undamaged sister copy of the DNA as a template to make a perfect repair, ensuring no genetic information is lost.

This repair mechanism is fundamental for preserving genomic stability. The BRCA1 protein, for example, interacts with other proteins to form a complex that carries out these repairs. By mending these breaks accurately, the BRCA proteins prevent the accumulation of genetic errors. This function in DNA repair is how they help to prevent cells from progressing towards a cancerous state.

Impact of BRCA Mutations

When a person has a harmful change, or mutation, in one of their BRCA genes, the resulting protein may be faulty or not produced at all. This compromises the cell’s ability to effectively repair DNA damage. The machinery designed to fix double-strand breaks through homologous recombination can no longer function properly, leading to an accumulation of genetic errors.

Without the precise repair directed by BRCA proteins, cells may resort to alternative, more error-prone repair pathways to fix DNA breaks. These backup systems can introduce small errors each time they are used. Over time, these mistakes build up within the cell’s genetic code. This state of increasing genetic disarray is referred to as genomic instability.

This instability is the consequence of a non-functional BRCA gene. The cell’s DNA becomes increasingly corrupted with each division. This accumulation of DNA damage sets the stage for more significant problems, as the errors can begin to affect other genes that regulate essential cellular processes.

From Mutation to Cancer Risk

The genomic instability caused by faulty BRCA genes is a direct link to an elevated cancer risk. As a cell with a BRCA mutation divides, the accumulated DNA errors can eventually affect genes that control cell growth and division. If these control genes are damaged, a cell can begin to proliferate without the normal checks and balances, leading to the formation of a tumor. This is why inheriting a BRCA mutation significantly increases a person’s lifetime risk for developing certain types of cancer.

The cancers most strongly associated with BRCA mutations are breast and ovarian cancer. A harmful BRCA1 or BRCA2 variant also increases the risk of developing prostate and pancreatic cancer. The reason some tissues are more susceptible than others is not fully understood, but it may be related to the specific roles of BRCA proteins in those tissues or hormonal influences that affect cell growth. For instance, breast cancers in people with BRCA1 mutations are often a type that is more difficult to treat.

The loss of this DNA repair function allows for the genetic damage that can result in cancer. The specific type of cancer that develops may be influenced by a combination of genetic and environmental factors.

Inheritance and Genetic Predisposition

BRCA gene mutations are hereditary and are passed down through families in a pattern known as autosomal dominant inheritance. This means that a mutation in just one copy of the gene, inherited from either parent, is sufficient to increase cancer risk. Every child of a parent who carries a BRCA mutation has a 50% chance of inheriting that same mutation.

Inheriting a BRCA mutation does not mean that an individual is guaranteed to develop cancer. It signifies that their lifetime risk is substantially higher than that of someone without the mutation. A person inherits one faulty copy of the gene, but the second copy in each cell remains normal and functional, which protects the cell initially. Cancer typically develops only after the second, normal copy of the gene becomes damaged or lost in a specific cell during a person’s lifetime, a concept known as the “second hit.”

This genetic predisposition explains why certain cancers can appear to run in families. A BRCA mutation passed from generation to generation increases the likelihood that family members will develop related cancers, often at younger ages. Understanding this inheritance pattern is a component of assessing cancer risk and making informed decisions about genetic testing and preventative strategies.