Difference Between BRCA1 and BRCA2 Gene

The main difference between BRCA1 and BRCA2 gene is that a mutation in BRCA1 gene has more risk of ovarian cancer whereas a mutation in BRCA2 gene has an increased risk of pancreatic cancer and melanoma. Furthermore, BRCA2 mutations have an increased risk of prostate as well as breast cancers in men.

BRCA1 and BRCA2 are two types of tumor suppressor genes, which prevent the development of cancers.   

Key Areas Covered

1. What is BRCA1 Gene
     – Definition, Role, Mutations
2. What is BRCA2 Gene
     – Definition, Role, Mutations
3. What are the Similarities Between BRAC1 and BRCA2 Gene
     – Outline of Common Features
4. What is the Difference Between BRCA1 and BRCA2 Gene
     – Comparison of Key Differences

Key Terms

BRAC1 Gene, BRCA2 Gene, Cancer Development, Mutations

What is BRCA1 Gene

BRCA1 (Breast Cancer 1) is a type of tumor suppressor gene encoded for a nuclear phosphoprotein that maintains genomic stability. This gene product is involved in the formation of a large multi-subunit protein called BRCA1-associated genome surveillance complex (BASC) with other tumor suppressor genes and DNA damage sensors. Also, the gene product of BRCA1 interacts with histone deacetylase complexes by associating with RNA polymerase II. It has a role in transcription, recombination, and DNA repair of double-stranded breaks as well.

Figure 1: Domains of the BRCA1 Gene Product

The regulation of the expression of the BRCA1 gene occurs mainly through alternative splicing by modulating the physiological function and the subcellular localization. The mutated gene product of BRCA1 gene is responsible for around 40% of inherited breast cancers and over 80% of inherited ovarian and breast cancers.

What is BRCA2 Gene

BRCA2 (Breast Cancer 2) is another type of tumor suppressor gene which confers an increased lifetime risk of developing breast or ovarian cancer upon mutation. The gene product of BRCA2 is responsible for the DNA repair of double-strand breaks through homologous recombination pathway. Several copies of 70 amino acids long BRC motifs bind to the RAD51 recombinase, which is involved in DNA repair.

Figure 2: Recombination Repair of DNA Double-Strand Damage

Mutations in the BRCA2 gene predispose to breast and ovarian cancer upon mutation. It is responsible for a significant fraction of early-onset prostate cancer in men.

Similarities Between BRAC1 and BRCA2 Gene

• BRCA1 and BRCA2 are two types of tumor suppressor genes.
• The main function of these genes is to stabilize the cell’s DNA while controlling the cell growth. Hence, both play a critical role in preventing the development.
• They also maintain the double-strand DNA repair through homologous recombination pathway.
• Mutations in both genes may lead to the development of cancers.

Difference Between BRCA1 and BRCA2 Gene

Definition

BRCA1 refers to a gene that normally acts to restrain the growth of cells in the breast but which, when mutated, predisposes to breast cancer while BRCA2 refers to a tumor suppressor gene, which confers an increased lifetime risk of developing breast or ovarian cancer.

Location

A BRCA1 gene occurs on chromosome 17q21 while the BRCA2 gene occurs on the chromosome 13q12.3.

Mutations

The mutated BRCA1 gene has an increased risk of ovarian cancer while the mutated BRCA2 gene has an increased risk of pancreatic cancer and melanoma. This is one main difference between BRCA1 and BRCA2 gene.

Prognosis

BRCA1 gene has a worse prognosis upon mutation while the BRCA2 gene has a lesser worse prognosis upon mutation.

Conclusion

The BRCA1 is a type of tumor suppressor gene with an increased risk of ovarian cancers while BRCA2 is another type of tumor suppressor gene with an increased risk of pancreatic cancer and melanoma. The BRCA1 gene is at the chromosome 17 while the BRCA2 gene is to the chromosome 13. The main difference between BRCA1 and BRCA2 gene is the type of cancer development and the location within the chromosomes.

Reference:

1. “Definition of BRCA2.” MedicineNet, Available Here
2. “BRCA1 Gene – Genetics Home Reference – NIH.” U.S. National Library of Medicine, National Institutes of Health, Available Here

Image Courtesy:

1. “BRCA1partB” By Clark et al; Part B Cropped from original Fig 1 by SLE346_B3 – (CC BY-SA 3.0) via Commons Wikimedia 
2. “Homologous recombinational repair of DNA double-strand damage” By Chaya5260 – Own work (CC BY-SA 4.0) via Commons Wikimedia