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

Autori
Ribes-Zamora, Albert ; Indiviglio, Sandra M. ; Mihalek, Ivana ; Williams, Christopher L. ; Bertuch, Alison A.

Izvornik
Cell Reports (2211-1247) 5 (2013), 1; 194-206

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
TRF2, Ku, NHEJ, telomeres

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Biotehnologija, Interdisciplinarne biotehničke znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA