| First Author | Kibe T | Year | 2016 |
| Journal | Mol Cell | Volume | 61 |
| Issue | 2 | Pages | 236-46 |
| PubMed ID | 26778124 | Mgi Jnum | J:233038 |
| Mgi Id | MGI:5780636 | Doi | 10.1016/j.molcel.2015.12.016 |
| Citation | Kibe T, et al. (2016) TPP1 Blocks an ATR-Mediated Resection Mechanism at Telomeres. Mol Cell 61(2):236-46 |
| abstractText | The regulation of 5' end resection at DSBs and telomeres prevents genome instability. DSB resection is positively and negatively regulated by ATM signaling through CtIP/MRN and 53BP1-bound Rif1, respectively. Similarly, telomeres lacking TRF2 undergo ATM-controlled CtIP-dependent hyper-resection when the repression by 53BP1/Rif1 is alleviated. However, telomere resection in the absence of 53BP1/Rif1 is more extensive upon complete removal of shelterin, indicating additional protection against resection by shelterin. Here we show that TPP1 and POT1a/b in shelterin block a resection pathway distinct from that repressed by TRF2. This second pathway is regulated by ATR signaling, involves Exo1 and BLM, and is inhibited by 53BP1/Rif1. Thus, mammalian cells have two distinct 5' end-resection pathways that are regulated by DNA damage signaling, in part through Rif1-mediated inhibition. The data show that telomeres are protected from hyper-resection through the repression of the ATM and ATR kinases by TRF2 and TPP1-bound POT1a/b, respectively. |
