Apollo contributes to G overhang maintenance and protects leading-end telomeres Journal Article
| Authors: | Wu, P.; Van Overbeek, M.; Rooney, S.; De Lange, T. |
| Article Title: | Apollo contributes to G overhang maintenance and protects leading-end telomeres |
| Abstract: | 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. © 2010 Elsevier Inc. |
| Keywords: | controlled study; unclassified drug; gene deletion; mutation; dna-binding proteins; nonhuman; dna replication; dna synthesis; proteins; animal cell; mouse; phenotype; telomere; mammalia; animals; cell cycle proteins; mice; mice, knockout; dna damage; cell cycle s phase; cell line; protein binding; genotype; rna interference; enzyme activation; mice, inbred c57bl; time factors; dna; protein-serine-threonine kinases; tumor suppressor proteins; gene fusion; fibroblasts; atm protein; nuclease; cellcycle; nucleic acid conformation; s phase; amino acid motifs; g2 phase; telomere-binding proteins; telomeric repeat binding protein 2; apollo protein |
| Journal Title: | Molecular Cell |
| Volume: | 39 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2010-08-01 |
| Start Page: | 606 |
| End Page: | 617 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2010.06.031 |
| PUBMED: | 20619712 |
| PROVIDER: | scopus |
| PMCID: | PMC2929323 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 20 April 2011" - "CODEN: MOCEF" - "Source: Scopus" |
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