Abstract

The ends of human chromosomes are characterised by specific arrays of TTAGGG repeats at the telomeres. A complex formed by six-proteins (called Shelterin), specifically recognises these regions (Palm and de Lange, 2008). This complex allows cells to distinguish telomeres from sites of DNA damage.

The components of shelterin were gradually identified over the past 10 years. There are essentially six core shelterin subunits: TRF1, TRF2, TIN2, RAP1, TPP1, and POT1. TRF1, TRF2 and POT1 have DNA-binding domains and directly recognize the human chromosome ends. For the shelterin-associated proteins they are recruited to telomeres through interaction with TRF1 or TRF2. TRF2 is also implicated in the regulation of DNA repair processes.

TRF1 and TRF2 are paralogues with almost the same molecular architecture, yet they interact with different protein sets. They are composed of a C-terminal DNA-binding SANT domain, a dimerisation and protein-interacting TRFH domain (PF08558) and natively disordered linkers. The interaction of the shelterin protein TIN2 with TRF1 TRFH was narrowed down to an FxLxP-based motif which binds in part by anti-parallel beta augmentation (Chen et al., 2008). A similar YxLxP motif in the shelterin accessory factor Apollo (SNM1B) binds equivalently to the TRF2 TFRH. It is thought that the motif binding pockets dictate the specificity for the F and Y residues. TRF1 also interacts with an FxLxP motif in the shelterin associated factor PinX1.