TRF2

TRF2, or telomeric repeat-binding factor 2, is a protein encoded by the TERF2 gene in humans. It is a core component of the shelterin complex, a six-protein assembly that binds telomeres and protects chromosome ends from being recognized as DNA damage. TRF2 binds double-stranded telomeric DNA through its C-terminal DNA-binding domain and forms dimers via its central dimerization domain, enabling stable association with telomere repeats.

Within shelterin, TRF2 coordinates with other components such as TRF1, TIN2, POT1, TPP1, and RAP1 to cap telomeres, regulate the architecture of the telomeric end, and suppress inappropriate DNA damage signaling. A key role of TRF2 is to help maintain the T-loop structure, which sequesters telomere ends and prevents activation of the ATM-dependent DNA damage response. By doing so, TRF2 protects against chromosome end fusions and genomic instability.

Loss or depletion of TRF2 leads to telomere deprotection, accumulation of telomere-specific DNA damage foci, end-to-end chromosome fusions, and cell cycle arrest or cell death. TRF2 expression is developmentally regulated and is particularly important in cells with active telomere maintenance; dysregulation of TRF2 has been associated with aging-related phenotypes and cancer biology.

Discovery and study of TRF2 are centered in vertebrate telomere biology, where it is recognized as a key guardian of chromosome end integrity within the shelterin complex.