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

我们的细胞含有DNA，即所谓的“生命的遗传蓝图”，它为我们的基因编码信息。DNA具有简单的重复结构，由两条互补的DNA链组成，形成双螺旋结构。DNA的完整性不断受到各种DNA损伤剂的挑战。这些物质包括来自太阳的高能紫外线和x射线辐射，人造和环境的化学物质，甚至我们呼吸的氧气都会攻击和破坏DNA。近年来，人们已经意识到，我们自己的细胞会产生大量负责修复这种DNA损伤的蛋白质，如果不加以控制，就会导致癌症等疾病的发展。这些蛋白质“机器”可以剪切和替换异常的DNA突变/结构，并将断裂的DNA链拼接在一起。其中一种蛋白质被称为DNA连接酶，它与它的伙伴蛋白：Ku、聚合酶和核酸酶相互作用，形成DNA断裂修复复合体。这种修复装置能够检测到DNA螺旋中的物理断裂，将末端重新组合在一起，如果需要的话重新塑造它们，最后重新密封这些断裂，以恢复双链DNA的连续性。这项工作的重点是了解这些修复复合体如何在密封步骤之前弥合断裂并使DNA末端重新组合在一起。

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.