Research Highlight Identity Crisis When Telomeres Left Unprotected

Loss of shelterin components TRF2 or POT1a–TPP1 complex from the chromosome end triggers DNA damage response (DDR) and aberrant DNA repair events. In a recent Nature paper, Chang and colleagues reported that the DNA repair protein Mre11 contributes to multiple events at the uncapped telomere, including ataxia telangiectasia-mutated (ATM)-dependent signaling, processing of the telomeric G-tail and homologous recombination (HR). The terminus of most eukaryotic chromo-somes forms a specialized structure called the telomere, which resolves two challenges faced by linear chromosomes: the end replication problem and the neces-sity to protect chromosome ends from erroneous recognition and repair as DNA double-strand breaks (DSBs). The mamma-lian telomere is hypothesized to be orga-nized into a unique lariat-like structure (t-loop) (Griffith et al., 1999), formed b