TRF2 Interaction with Ku Heterotetramerization Interface Gives Insight into c-NHEJ Prevention at Human Telomeres

25Citations
Citations of this article
62Readers
Mendeley users who have this article in their library.

Abstract

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

Cite

CITATION STYLE

APA

Ribes-Zamora, A., Indiviglio, S. M., Mihalek, I., Williams, C. L., & Bertuch, A. A. (2013). TRF2 Interaction with Ku Heterotetramerization Interface Gives Insight into c-NHEJ Prevention at Human Telomeres. Cell Reports, 5(1), 194–206. https://doi.org/10.1016/j.celrep.2013.08.040

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free