Kanaar Roland, Wyman Claire, Rothstein Rodney
Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
EMBO J. 2008 Feb 20;27(4):581-8. doi: 10.1038/emboj.2008.11.
DNA ends pose specific problems in the control of genetic information quality. Ends of broken DNA need to be rejoined to avoid genome rearrangements, whereas natural DNA ends of linear chromosomes, telomeres, need to be stable and hidden from the DNA damage response. Efficient DNA end metabolism, either at induced DNA breaks or telomeres, does not result from the machine-like precision of molecular reactions, but rather from messier, more stochastic processes. The necessary molecular interactions are dynamically unstable, with constructive and destructive processes occurring in competition. In the end, quality control comes from the constant building up and tearing down of inappropriate, but also appropriate reaction steps in combination with factors that only slightly shift the equilibrium to eventually favour appropriate events. Thus, paradoxically, enzymes antagonizing DNA end metabolism help to ensure that genome maintenance becomes a robust process.
DNA末端在遗传信息质量控制方面存在特定问题。断裂DNA的末端需要重新连接以避免基因组重排,而线性染色体的天然DNA末端,即端粒,需要保持稳定并免受DNA损伤反应的影响。无论是在诱导的DNA断裂处还是端粒处,高效的DNA末端代谢并非源于分子反应如机器般的精确性,而是源于更混乱、更具随机性的过程。必要的分子相互作用是动态不稳定的,建设性和破坏性过程相互竞争。最终,质量控制来自于不断地构建和拆解不适当但也包括适当的反应步骤,以及一些仅轻微改变平衡以最终有利于适当事件的因素。因此,矛盾的是,拮抗DNA末端代谢的酶有助于确保基因组维护成为一个稳健的过程。