Bloom syndrome protein

Bloom syndrome protein (BLM) is a protein that plays a critical role in the maintenance of genetic stability in cells. It is encoded by the BLM gene in humans. Mutations in this gene can lead to Bloom syndrome, a rare autosomal recessive disorder characterized by short stature, predisposition to the development of cancer, and chromosomal instability.

Function

The Bloom syndrome protein is a RecQ helicase, which is a type of DNA helicase. DNA helicases are enzymes that unwind DNA double helices, a critical step in DNA replication, repair, and recombination processes. Specifically, BLM resolves DNA structures that can be problematic for DNA replication, such as DNA loops and G-quadruplexes. By doing so, it helps to prevent DNA damage and maintain chromosomal stability.

BLM also interacts with several other proteins involved in DNA repair and replication, including BRCA1, MLH1, and RAD51, to form a complex that ensures the accuracy of these processes. Its role in homologous recombination, a type of genetic recombination used by cells to repair harmful breaks in DNA, is particularly important for preventing genomic instability.

Clinical Significance

Mutations in the BLM gene lead to Bloom syndrome. Individuals with this condition exhibit a high frequency of chromosomal aberrations, such as increased sister chromatid exchanges, which are indicative of genomic instability. This instability is believed to be a key factor in the predisposition of Bloom syndrome patients to develop various types of cancer at an early age.

In addition to cancer predisposition, Bloom syndrome is associated with several other clinical features, including growth retardation, immunodeficiency, and a characteristic facial appearance with sun-sensitive skin lesions. There is currently no cure for Bloom syndrome, and management focuses on surveillance and treatment of symptoms and complications, particularly malignancies.

Genetic and Molecular Aspects

The BLM gene is located on chromosome 15 (15q26.1). It spans more than 150 kilobases and consists of 23 exons. The protein encoded by the BLM gene has 1,417 amino acids and belongs to the RecQ helicase family, which includes several other helicases involved in DNA repair and maintenance.

Research into the BLM protein and its interactions with other proteins involved in DNA repair pathways continues to provide insights into the mechanisms of genomic stability and the causes of genomic instability in cancer and other diseases. Understanding the function of BLM and its role in DNA repair and replication may lead to new therapeutic strategies for diseases associated with genomic instability.

See Also

• DNA repair
• Genetic disorder
• Helicase
• RecQ helicase family