| First Author | Wu P | Year | 2010 |
| Journal | Mol Cell | Volume | 39 |
| Issue | 4 | Pages | 606-17 |
| PubMed ID | 20619712 | Mgi Jnum | J:163935 |
| Mgi Id | MGI:4830207 | Doi | 10.1016/j.molcel.2010.06.031 |
| Citation | Wu P, et al. (2010) Apollo contributes to G overhang maintenance and protects leading-end telomeres. Mol Cell 39(4):606-17 |
| abstractText | Mammalian telomeres contain a single-stranded 3' overhang that is thought to mediate telomere protection. Here we identify the TRF2-interacting factor Apollo as a nuclease that contributes to the generation/maintenance of this overhang. The function of mouse Apollo was determined using Cre-mediated gene deletion, complementation with Apollo mutants, and the TRF2-F120A mutant that cannot bind Apollo. Cells lacking Apollo activated the ATM kinase at their telomeres in S phase and showed leading-end telomere fusions. These telomere dysfunction phenotypes were accompanied by a reduction in the telomeric overhang signal. The telomeric functions of Apollo required its TRF2-interaction and nuclease motifs. Thus, TRF2 recruits the Apollo nuclease to process telomere ends synthesized by leading-strand DNA synthesis, thereby creating a terminal structure that avoids ATM activation and resists end-joining. These data establish that the telomeric overhang is required for the protection of telomeres from the DNA damage response. |
