Different components of shelterin are dedicated to different aspects of the end-protection problem

Different components of shelterin are dedicated to different aspects of the end-protection problem. TRF2 represses the ATM kinase signaling pathway (A), whereas POT1 ensures that the ATR kinase is not activated (B). In addition, TRF2 is the main repressor of NHEJ at telomeres, although POT1 contributes to the repression of NHEJ, especially after DNA replication. Both TRF2 and POT1 function to block HDR at telomeres (not shown). TRF2 is proposed to block NHEJ and ATM kinase signaling by forming the t-loop. In the t-loop structure (A), the telomere end is hidden from the DNA end sensor MRN that activates the ATM kinase pathway (MRN), and the Ku70/80 ring (which initiates NHEJ) will not be able to load onto the chromosome end. In (B), POT1 is proposed to block ATR kinase signaling by preventing the binding of RPA, the single-stranded DNA binding protein that activates the ATR kinase pathway. POT1 could block RPA from binding to the single-stranded telomeric DNA either when present at the telomere terminus (as shown) or when exposed in the D loop of the t-loop configuration.

Publication

How Telomeres Solve the End-Protection Problem. () Titia de Lange. Science. ;326(5955):948. Figure: F3. All organisms Drosophila melanogaster Homo sapiens Gallus gallus Mus musculus Xenopus laevis Arabidopsis thaliana

Disease mentions