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 [1, 2]. The human telomeric protein TRF2 coordinates several pathways that prevent checkpoint activation and chromosome fusions [3-9]. In this work, we identified hSNM1B [10], 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 [11]. Both proteins belong to the P-CASP metallo-beta-lactamase family of DNA caretaker proteins [12, 13]. 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.