TableEdit

Ribes-Zamora, A, Indiviglio, SM, Mihalek, I, Williams, CL and Bertuch, AA (2013) TRF2 interaction with Ku heterotetramerization interface gives insight into c-NHEJ prevention at human telomeres. Cell Rep 5:194-206

Telomeres are protected from nonhomologous end-joining (NHEJ) to avoid deleterious chromosome fusions, yet they associate with the Ku heterodimer that is principal in the classical NHEJ (c-NHEJ) pathway. T-loops have been proposed to inhibit Ku's association with telomeric ends, thus inhibiting c-NHEJ; however, deficiencies in the t-loop model suggest additional mechanisms are in effect. We demonstrate that TRF2 interacts with Ku at telomeres and via residues in Ku70 helix 5 (α5), which are vital for NHEJ. We show that Ku's interaction with a TRF2 mutant that induces telomeric fusions is significantly impaired. Additionally, we demonstrate that Ku70 α5 is required for Ku self-association in live cells, which can bridge DNA ends. Together, these findings lead us to propose a model in which telomeres are directly protected from c-NHEJ via TRF2 impeding Ku's ability to synapse telomere ends.

PubMed PMC3984498 Online version:10.1016/j.celrep.2013.08.040

Antigens, Nuclear/chemistry; Antigens, Nuclear/genetics; Antigens, Nuclear/metabolism; DNA End-Joining Repair; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Humans; Ku Autoantigen; Models, Molecular; Protein Multimerization; Recombination, Genetic; Telomere/chemistry; Telomere/genetics; Telomere/metabolism; Telomeric Repeat Binding Protein 2/genetics; Telomeric Repeat Binding Protein 2/metabolism