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-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.
Lenain
Christelle
C
Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, Centre National de la Recherche Scientifique, Unité mixte de recerche 5161, Institut Fédératif de Recherche 128, 46 Allée d'Italie, F-69364 Lyon, France.
Bauwens
Serge
S
Amiard
Simon
S
Brunori
Michele
M
Giraud-Panis
Marie-Josèphe
MJ
Gilson
Eric
E
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes; D005090:Exodeoxyribonucleases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000032:analysis; D016615:Telomere / Q000378:metabolism* / Q000648:ultrastructure; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*
D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D035341:Telomeric Repeat Binding Protein 2; D005982:Glutathione Transferase; C493741:DCLRE1B protein, human; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes