The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair

A major issue in telomere research is to understand how the integrity of chromosome ends is preserved . The human telomeric protein TRF2 coordinates several pathways that prevent checkpoint activation and chromosome fusions. In this work, we identified hSNM1B, here named Apollo, as a novel TRF2-inte...

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Veröffentlicht in:Current biology Jg. 16; H. 13; S. 1303
Hauptverfasser: Lenain, Christelle, Bauwens, Serge, Amiard, Simon, Brunori, Michele, Giraud-Panis, Marie-Josèphe, Gilson, Eric
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 11.07.2006
Schlagworte:
Animals
Chlorocebus aethiops
COS Cells
DNA Repair - physiology
DNA Repair Enzymes
Exodeoxyribonucleases - analysis
Exodeoxyribonucleases - genetics
Exodeoxyribonucleases - physiology
Glutathione Transferase - analysis
Humans
Nuclear Proteins - analysis
Nuclear Proteins - genetics
Nuclear Proteins - physiology
Recombinant Fusion Proteins - analysis
Telomere - metabolism
Telomere - ultrastructure
Telomeric Repeat Binding Protein 2 - metabolism
ISSN:0960-9822
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Zusammenfassung:A major issue in telomere research is to understand how the integrity of chromosome ends is preserved . The human telomeric protein TRF2 coordinates several pathways that prevent checkpoint activation and chromosome fusions. In this work, we identified hSNM1B, here named Apollo, as a novel TRF2-interacting factor. Interestingly, the N-terminal domain of Apollo is closely related to that of Artemis, a factor involved in V(D)J recombination and DNA repair. Both proteins belong to the beta-CASP metallo-beta-lactamase family of DNA caretaker proteins. Apollo appears preferentially localized at telomeres in a TRF2-dependent manner. Reduced levels of Apollo exacerbate the sensitivity of cells to TRF2 inhibition, resulting in severe growth defects and an increased number of telomere-induced DNA-damage foci and telomere fusions. Purified Apollo protein exhibits a 5'-to-3' DNA exonuclease activity. We conclude that Apollo is a novel component of the human telomeric complex and works together with TRF2 to protect chromosome termini from being recognized and processed as DNA damage. These findings unveil a previously undescribed telomere-protection mechanism involving a DNA 5'-to-3' exonuclease.
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ISSN:0960-9822
DOI:10.1016/j.cub.2006.05.021