Marcand S, Wotton D, Gilson E, Shore D
Department of Microbiology, College of Physicians & Surgeons of Columbia University, NY 10032, USA.
Ciba Found Symp. 1997;211:76-93; discussion 93-103. doi: 10.1002/9780470515433.ch6.
Telomere length in the yeast Saccharomyces cerevisiae is under stringent genetic control such that a narrow length distribution of TG1-3 repeats is observed. Previous studies have shown that Rap1p, which binds to the double-stranded telomeric repeats, plays a role in regulating repeat length: point mutations in the Rap1p C-terminus often result in a higher average telomere length and deletion of this region causes extreme telomere elongation. We have investigated further the role of Rap1p in this process. Our results suggest that telomere length is regulated by a negative feedback mechanism that can sense the number of Rap1p molecules bound at the chromosome end. This length regulatory mechanism requires two other proteins, Rif1p and Rif2p, that interact with each other and with the Rap1p C-terminus. Although the same C-terminal domain of Rap1p is also involved in the initiation of telomere position effect (telomeric transcriptional silencing), this Rap1p function appears to be separate from, and indeed antagonistic to, its role in telomere length regulation.
酿酒酵母中的端粒长度受到严格的遗传控制,因此观察到TG1-3重复序列的长度分布较窄。先前的研究表明,与双链端粒重复序列结合的Rap1p在调节重复序列长度中发挥作用:Rap1p C末端的点突变通常会导致平均端粒长度增加,而该区域的缺失会导致端粒极度延长。我们进一步研究了Rap1p在此过程中的作用。我们的结果表明,端粒长度受负反馈机制调节,该机制可以感知结合在染色体末端的Rap1p分子数量。这种长度调节机制需要另外两种蛋白质Rif1p和Rif2p,它们相互作用并与Rap1p C末端相互作用。尽管Rap1p的相同C末端结构域也参与端粒位置效应(端粒转录沉默)的起始,但这种Rap1p功能似乎与其在端粒长度调节中的作用分开,实际上是相互拮抗的。