Featherstone C, Jackson S P
Wellcome/Cancer Research Campaign Institute, Cambridge University, UK.
Mutat Res. 1999 May 14;434(1):3-15. doi: 10.1016/s0921-8777(99)00006-3.
The Ku protein binds to DNA ends and other types of discontinuity in double-stranded DNA. It is a tightly associated heterodimer of approximately 70 kDa and approximately 80 kDa subunits that together with the approximately 470 kDa catalytic subunit, DNA-PKcs, form the DNA-dependent protein kinase. This enzyme is involved in repairing DNA double-strand breaks (DSBs) caused, for example, by physiological oxidation reactions, V(D)J recombination, ionizing radiation and certain chemotherapeutic drugs. The Ku-dependent repair process, called illegitimate recombination or nonhomologous end joining (NHEJ), appears to be the main DNA DSB repair mechanism in mammalian cells. Ku itself is probably involved in stabilizing broken DNA ends, bringing them together and preparing them for ligation. Ku also recruits DNA-PKcs to the DSB, activating its kinase function. Targeted disruption of the genes encoding Ku70 and Ku80 has identified significant differences between Ku-deficient mice and DNA-PKcs-deficient mice. Although all three gene products are clearly involved in repairing ionizing radiation-induced damage and in V(D)J recombination, Ku-knockout mice are small, and their cells fail to proliferate in culture and show signs of premature senescence. Recent findings have implicated yeast Ku in telomeric structure in addition to NHEJ. Some of the phenotypes of the Ku-knockout mice may indicate a similar role for Ku at mammalian telomeres.
Ku蛋白可与双链DNA的末端及其他类型的双链间断处结合。它是一种紧密结合的异源二聚体，由大约70 kDa和大约80 kDa的亚基组成，该异源二聚体与大约470 kDa的催化亚基DNA依赖蛋白激酶催化亚基（DNA-PKcs）共同构成DNA依赖蛋白激酶。这种酶参与修复例如由生理氧化反应、V(D)J重组、电离辐射及某些化疗药物所导致的DNA双链断裂（DSB）。依赖Ku的修复过程，称为异常重组或非同源末端连接（NHEJ），似乎是哺乳动物细胞中主要的DNA双链断裂修复机制。Ku自身可能参与稳定断裂的DNA末端，使其聚集并为连接做准备。Ku还可将DNA-PKcs募集至双链断裂处，激活其激酶功能。对编码Ku70和Ku80的基因进行靶向破坏已明确了Ku缺陷小鼠与DNA-PKcs缺陷小鼠之间的显著差异。尽管所有这三种基因产物均明显参与修复电离辐射诱导的损伤及V(D)J重组，但Ku基因敲除小鼠体型较小，其细胞在培养中无法增殖，并表现出早衰迹象。最近的研究结果表明，除了非同源末端连接外，酵母Ku还参与端粒结构。Ku基因敲除小鼠的一些表型可能表明Ku在哺乳动物端粒中具有类似作用。
