Karlseder Jan
Regulatory Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA92037, USA.
Cancer Lett. 2003 May 15;194(2):189-97. doi: 10.1016/s0304-3835(02)00706-1.
Per definition, a linear chromosome contains two ends, two sites, which by analogy to double-stranded breaks, might be expected to induce cell cycle checkpoints. The fact that cells divide without inducing such checkpoints suggests that telomeres, the natural ends of linear chromosomes, have the ability to suppress checkpoint activation. This suppression takes place at a number of levels. The TTAGGG repeats of human telomeric DNA recruit telomere specific proteins, among them the telomere repeat binding factors TRF1 and TRF2. These proteins, along with their interaction partners, reorganize the linear chromosome end into a t loop, a protected structure, which hides the very end of the chromosome. Here it is discussed how mammalian telomeres differ from DNA breaks, and what methods they use to prevent checkpoint activation.
根据定义,线性染色体有两个末端,这两个位点类似于双链断裂,可能会引发细胞周期检查点。细胞分裂时并未引发此类检查点,这一事实表明,线性染色体的天然末端——端粒,具有抑制检查点激活的能力。这种抑制发生在多个层面。人类端粒DNA的TTAGGG重复序列会招募端粒特异性蛋白,其中包括端粒重复序列结合因子TRF1和TRF2。这些蛋白与其相互作用伙伴一起,将线性染色体末端重新组织成t环,这是一种受保护的结构,隐藏了染色体的末端。本文将讨论哺乳动物端粒与DNA断裂的不同之处,以及它们用于防止检查点激活的方法。