| First Author | Takai KK | Year | 2011 |
| Journal | Mol Cell | Volume | 44 |
| Issue | 4 | Pages | 647-59 |
| PubMed ID | 22099311 | Mgi Jnum | J:178606 |
| Mgi Id | MGI:5299359 | Doi | 10.1016/j.molcel.2011.08.043 |
| Citation | Takai KK, et al. (2011) Telomere Protection by TPP1/POT1 Requires Tethering to TIN2. Mol Cell 44(4):647-59 |
| abstractText | To prevent ATR activation, telomeres deploy the single-stranded DNA binding activity of TPP1/POT1a. POT1a blocks the binding of RPA to telomeres, suggesting that ATR is repressed through RPA exclusion. However, comparison of the DNA binding affinities and abundance of TPP1/POT1a and RPA indicates that TPP1/POT1a by itself is unlikely to exclude RPA. We therefore analyzed the central shelterin protein TIN2, which links TPP1/POT1a (and POT1b) to TRF1 and TRF2 on the double-stranded telomeric DNA. Upon TIN2 deletion, telomeres lost TPP1/POT1a, accumulated RPA, elicited an ATR signal, and showed all other phenotypes of POT1a/b deletion. TIN2 also affected the TRF2-dependent repression of ATM kinase signaling but not to TRF2-mediated inhibition of telomere fusions. Thus, while TIN2 has a minor contribution to the repression of ATM by TRF2, its major role is to stabilize TPP1/POT1a on the ss telomeric DNA, thereby allowing effective exclusion of RPA and repression of ATR signaling. |
