The structure of the Ku-DNA complex reveals that the Ku heterodimer forms a ring that encircles and cradles the end of the strand of DNA. We believe that the Ku proteins have to hold the DNA ends together, said Goldberg. The question is how they hold the end of a piece of DNA without obscuring the end. We found that our protein has an extensive base that cradles the DNA, with a very narrow bridge that lies over the top -- holding one side of the DNA extensively, but leaving the other side almost completely exposed. We think this exposure might allow other repair factors to act on the broken ends to repair them.

The scientists speculate that the Ku proteins on two broken ends link to one another to hold the two ends in position for joining the DNA back together. Goldberg and his colleagues also found that the Ku heterodimer makes no contact with the DNA bases, but rather grasps the sugar backbone of the DNA strand -- meaning that the protein does not care about the sequence of the DNA that it binds.

The scientists also have evidence that Ku holds the DNA in precise alignment to allow ready joining by repair enzymes. Its logical that if the protein precisely aligns the DNA ends, that gives an advantage to the repair proteins and the ligases that are going to ultimately join the DNA ends together, said Goldberg.

Next, Goldberg and his colleagues plan to explore the structure of the Ku proteins attached to two broken strands of DNA in order to understand the mechanism by which they precisely align the ends. This precision is a key to the accuracy of the joining process in the absence of natural homology of the separated strands that could aid repair, Goldberg said.

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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
8-Aug-2001