Ku heterodimer

Two proteins are initially involved in the nonho-mologous rejoining of a ds break. Ku, a heterodimer of 70 kDa and 86 kDa subunits, binds to free DNA ends and has latent ATP-dependent helicase activity. The DNA-bound Ku heterodimer recruits a unique protein kinase, DNA-dependent protein kinase (DNA-PK). DNA-PK has a binding site for DNA free ends and another for dsDNA just inside these ends. It therefore allows for the approximation of the two separated ends. The free end DNA-Ku-DNA-PK complex activates the kinase activity in the latter. DNA-PK reciprocally phos-phorylates Ku and the other DNA-PK molecule, on the opposing strand, in trans. DNA-PK then dissociates from the DNA and Ku, resulting in activation of the Ku helicase. This results in unwinding of the two ends. The unwound, approximated DNA forms base pairs the extra nucleotide tails are removed by an exonucle-... 

In NHEJ in eukaryotes, the Ku heterodimer binds to both ends of the double-strand break (32) and recruits DNA-PKcs and the ligase IV-XRCC4 heterodimer. These then ligate both ends of the double-strand break regardless of whether they actually come from the same chromosome (33). In NHEJ, Artemis is the end-processing nuclease (34) (Fig. 8). 

Walker JR, Corpina RA, Goldberg J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 2001 412 607-614. 

An important nuclear protein, conserved from yeast to mammals, is the Ku heterodimer. This protein binds to DNA and repairs double strand breaks caused by x-rays and other agents. The Ku heterodimer is essential in maintaining chromosome integrity. 

The two subunits of the Ku heterodimer comprise the second class of telomerase proteins. Ku is responsible for nonhomolo-gous end-joining of broken chromosomes, and initially it appeared odd or perhaps even dangerous that it would be telomere associated after all, telomeres protect chromosome ends from fusion events that result in genomic instabihty. A solution to this conundrum was recently provided by SteUwagen et al. [26], who showed that Ku binds directly to telomerase RNA and promotes the de novo addition of telomeres to broken chromosome ends, thereby helping... 

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