Ku binds telomeric DNA in vitro

Ku is a heterodimeric protein with high binding affinity for ends, nicks, a nd gaps in double-stranded DNA. Both in mammalian cells and in budding yeas t, Ku plays a role in nonhomologous end joining in the double strand break repair pathway. However, Ku has a more significant role in DNA repair in ma mmalian cells compared with yeast, in which a homology-dependent pathway is the predominant one. Recently Ku has been shown to be a likely component o f the telomeric complex in yeast, suggesting the possibility of a similar r ole for Ku at mammalian telomeres, However, long single-stranded G-rich ove rhangs are continuously present at mammalian but not at yeast telomeres. Th ese overhangs have the potential to fold in vitro into G-G base-paired conf ormations, such as G-quartets, that might prevent Ku from recognizing telom eric ends and thus offer a mechanism to sequester the telomere from the pre valent double strand break repair pathway in mammals. We show here that Ku binds to mammalian telomeric DNA ends in vitro and that G-quartet conformat ions are unable to prevent Ku from binding with high affinity to the DNA, O ur results indicate that the DNA binding characteristics of Ku are consiste nt with its direct interaction with telomeric DNA in mammalian cells and it s proposed role as a telomere end factor.