FIGURE 5-39 Nonhomologous end joining. (a) When sister chromatids are not available to help repair double-strand breaks, nucleotide sequences are butted together that were not apposed in the unbroken DNA. These DNA ends are usually from the same chromosome locus, and when linked together, several base pairs are lost. Occasionally, ends from different chromosomes are accidentally joined together. A complex of two proteins, Ku and DNA-dependent protein kinase (DNA-PK), binds to the ends of a double-strand break (step 1). After formation of a synapse, the ends are further processed by nucleases, resulting in removal of a few bases (step 2), and the two double-stranded molecules are ligated together (step 3). As a result, the double-strand break is repaired, but several base pairs at the site of the break are removed. See G. Chu, 1997, J. Biol. Chem. 272:24097; M. Lieber et al., 1997, Curr. Opin. Genet. Devel. 7:99; and D. van Gant et al., 2001, Nature Rev. Genet. 2:196. (b) Structure of KU70/KU80 bound to a duplex DNA end. The complex is shown in a view down the DNA axis (left) and from the side (right). KU80 is light green, KU70 dark green, DNA blue.

[Part (b) data from J. R. Walker, R. A. Corpina, and J. Goldberg, 2001, Nature 412:607, PDB ID 1jey.]