The RAD51C gene plays a fundamental role in maintaining the integrity of our genetic material. It is a “cancer protection” gene, normally working to prevent the uncontrolled growth of cells that can lead to cancer. A mutation in this gene can disrupt its normal activity, increasing an individual’s susceptibility to certain health conditions.
How RAD51C Repairs DNA
The RAD51C gene produces a protein that is involved in a specific type of DNA repair called homologous recombination. This process is like a sophisticated cellular repair crew that fixes serious damage to DNA, particularly double-strand breaks where both strands of the DNA helix are severed. Imagine DNA as a ladder, and a double-strand break means both sides of the ladder are cut clean through. Homologous recombination uses an undamaged copy of the DNA as a template to accurately mend these breaks, ensuring that the genetic information is perfectly restored.
The RAD51C protein works as part of larger protein complexes. These complexes are central to both the early and late stages of homologous recombination, acting as molecular scaffolds and guides to facilitate the precise repair of damaged DNA. This meticulous repair process is crucial because even small errors or unrepaired breaks in the genetic code can lead to instability within the genome, which is a hallmark of many diseases, including cancer.
RAD51C and Cancer Risk
Mutations in the RAD51C gene significantly increase an individual’s risk for certain types of cancer, particularly ovarian cancer and, to a lesser extent, breast cancer. When RAD51C is faulty, the cell’s ability to perform accurate DNA repair through homologous recombination is compromised. This inability to fix DNA damage effectively allows errors to accumulate in the genetic code, driving cells towards uncontrolled growth and tumor formation.
For women, a faulty RAD51C gene increases the lifetime risk of ovarian cancer to approximately 8% by age 80, compared to about 0.9% in the general population. The lifetime risk for breast cancer in women with a RAD51C mutation is around 20% by age 80, whereas the general population risk is about 10.8%. These breast cancers are also more likely to be triple-negative breast cancer (TNBC), which lacks certain hormone receptors and HER2 expression. The association with these cancers highlights RAD51C’s role as a tumor suppressor gene.
Inheriting RAD51C Mutations
RAD51C mutations are typically inherited in an autosomal dominant pattern, meaning that a person only needs to inherit one copy of the mutated gene from either parent to have an increased risk of developing cancer. If one parent carries a RAD51C mutation, each child has a 50% chance of inheriting it. These inherited mutations are known as germline mutations, as they are present in every cell of the body, including reproductive cells, and can therefore be passed down through generations. Family history plays an important role in identifying individuals who might be at an increased risk, as the presence of multiple family members with ovarian or breast cancer could suggest an inherited RAD51C mutation within the family. In rare instances where both parents have a RAD51C mutation, their child could inherit two faulty copies, leading to a serious condition called Fanconi Anemia, which is characterized by birth defects, bone marrow failure, and an increased risk of childhood cancers.
Screening and New Treatments
Genetic testing is available to identify RAD51C mutations. These tests can help individuals understand their personal cancer risk and inform surveillance strategies. For those with a RAD51C mutation, cancer screenings may begin at a younger age or occur more frequently than for the general population.
Understanding the function of RAD51C in DNA repair has also opened avenues for personalized medicine, particularly with targeted therapies. For instance, PARP inhibitors are a class of drugs that can be effective for cancers with deficiencies in homologous recombination, such as those caused by RAD51C mutations. These treatments exploit the cell’s existing DNA repair defects, making it more difficult for cancer cells to survive and proliferate.