| First Author | Sfeir A | Year | 2012 |
| Journal | Science | Volume | 336 |
| Issue | 6081 | Pages | 593-7 |
| PubMed ID | 22556254 | Mgi Jnum | J:184522 |
| Mgi Id | MGI:5424278 | Doi | 10.1126/science.1218498 |
| Citation | Sfeir A, et al. (2012) Removal of shelterin reveals the telomere end-protection problem. Science 336(6081):593-7 |
| abstractText | The telomere end-protection problem is defined by the aggregate of DNA damage signaling and repair pathways that require repression at telomeres. To define the end-protection problem, we removed the whole shelterin complex from mouse telomeres through conditional deletion of TRF1 and TRF2 in nonhomologous end-joining (NHEJ) deficient cells. The data reveal two DNA damage response pathways not previously observed upon deletion of individual shelterin proteins. The shelterin-free telomeres are processed by microhomology-mediated alternative-NHEJ when Ku70/80 is absent and are attacked by nucleolytic degradation in the absence of 53BP1. The data establish that the end-protection problem is specified by six pathways [ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3 related) signaling, classical-NHEJ, alt-NHEJ, homologous recombination, and resection] and show how shelterin acts with general DNA damage response factors to solve this problem. |
