Bianchi Alessandro, Shore David
Department of Molecular Biology and National Centre of Competence in Research (NCCR) Frontiers in Genetics Program, University of Geneva, Sciences III, CH-1211 Geneva 4, Switzerland.
Genes Dev. 2007 Jul 15;21(14):1726-30. doi: 10.1101/gad.438907.
Telomere function is mediated by the assembly of a protein complex on an array of telomeric DNA (TG) repeats synthesized by the telomerase enzyme. Telomerase action at chromosome ends is finely tuned by the telomeric complex so that a constant average number of repeats is maintained. This is achieved through a negative feedback process that is sensitive to TG tract length, but whose underlying mechanism is unknown. We show that short telomeres, which are preferential substrates for telomerase, display increased association with the enzyme in the S phase of the cell cycle, when telomerase acts. In addition, we provide support for a molecular mechanism by which this key step of telomerase recruitment is regulated by TG tract length.
端粒功能由端粒酶合成的端粒DNA(TG)重复序列阵列上的蛋白质复合体组装介导。端粒复合体精细调节端粒酶在染色体末端的作用,从而维持重复序列的平均数量恒定。这是通过对TG序列长度敏感的负反馈过程实现的,但其潜在机制尚不清楚。我们发现,短端粒是端粒酶的优先底物,在端粒酶发挥作用的细胞周期S期,短端粒与该酶的结合增加。此外,我们为一种分子机制提供了支持,即端粒酶募集的这一关键步骤受TG序列长度调控。