Molecular basis for repairing DNA double-strand breaks by non homologous end-joining

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Our cells contain DNA, the so called "genetic blueprint of life" which encodes the information for our genes. DNA has a simple repeating structure composed of two complementary strands of DNA which form a double-helix structure. The integrity of DNA is constantly being challenged by various DNA-damaging agents. These agents include high energy UV and X-ray radiation from the sun, chemicals both man-made and environmental and even the oxygen we breathe can attack and damage DNA. In recent years it has been realised that our own cells produce a large number of proteins responsible for repairing this DNA damage which, if left unchecked, would lead to the development of conditions such as cancer. These protein "machines" can cut out and replace aberrant DNA mutations/structures and splice together broken DNA strands. One such protein is called DNA ligase, which interacts with its partner proteins: Ku , polymerase and nuclease to form a DNA break repair complex. This repair apparatus is able to detect physical breaks in the DNA helices, bring the ends back together, remodel them if required and, finally, reseal these breaks to restore the continuity of the double-strand DNA. The focus of this work is to understand how these repair complexes can bridge the break and make the DNA ends come back together prior to the sealing step.