TERF2

TERF2 or Telomeric Repeat Binding Factor 2 is a protein that in humans is encoded by the TERF2 gene. This protein is a key component of the shelterin complex, which is essential for telomere maintenance and protection. Telomeres are repetitive nucleotide sequences at the ends of chromosomes that protect them from degradation and fusion with neighboring chromosomes. As such, TERF2 plays a critical role in cellular aging, genome stability, and the prevention of cancer.

Function

TERF2, along with other shelterin complex proteins, binds to telomeres and regulates their length by controlling the access of telomerase, an enzyme that adds DNA sequence repeats to the ends of telomeres. This protein specifically binds to the double-stranded region of telomeres, distinguishing it from TERF1, which binds to both the double-stranded and single-stranded regions. By protecting the telomeres, TERF2 prevents the activation of DNA damage responses at chromosome ends, thereby allowing cells to divide without triggering senescence or apoptosis mechanisms prematurely.

Structure

The TERF2 protein contains several functional domains, including a homodimerization domain, which allows it to form dimers with itself or heterodimers with TERF1, and a DNA-binding domain that specifically recognizes the TTAGGG telomeric repeats. The interaction of TERF2 with other shelterin components and telomeric DNA is crucial for its role in telomere protection and length regulation.

Clinical Significance

Alterations in the TERF2 gene or its protein product can lead to telomere dysfunction, contributing to premature aging syndromes and increased susceptibility to cancer. Mutations that impair the protective function of TERF2 can lead to telomere shortening and the activation of DNA damage responses, resulting in genomic instability and the initiation of oncogenic pathways. Conversely, upregulation of TERF2 has been observed in certain types of cancer, where it contributes to the immortalization of cancer cells by maintaining telomere length and allowing continuous cell division.

Research

Ongoing research is focused on understanding the detailed mechanisms by which TERF2 regulates telomere protection and how its dysfunction contributes to disease. Studies are also exploring the potential of targeting TERF2 and other components of the shelterin complex in cancer therapy, aiming to induce telomere crisis in cancer cells and limit their proliferative capacity.

See Also

• Telomere
• Shelterin
• Telomerase
• DNA damage response
• Senescence
• Apoptosis
• Genomic instability
• Oncogene