Meng Fei-Long, Hu Yan, Shen Ning, Tong Xia-Jing, Wang Jianyong, Ding Jianping, Zhou Jin-Qiu
The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
EMBO J. 2009 May 20;28(10):1466-78. doi: 10.1038/emboj.2009.92. Epub 2009 Apr 16.
In budding yeast Saccharomyces cerevisiae, telomere length maintenance involves a complicated network as more than 280 telomere maintenance genes have been identified in the nonessential gene deletion mutant set. As a supplement, we identified additional 29 telomere maintenance genes, which were previously taken as essential genes. In this study, we report a novel function of Sua5p in telomere replication. Epistasis analysis and telomere sequencing show that sua5Delta cells display progressively shortened telomeres at early passages, and Sua5 functions downstream telomerase recruitment. Further, biochemical, structural and genetic studies show that Sua5p specifically binds single-stranded telomeric (ssTG) DNA in vitro through a distinct DNA-binding region on its surface, and the DNA-binding ability is essential for its telomere function. Thus, Sua5p represents a novel ssTG DNA-binding protein and positively regulates the telomere length in vivo.
在出芽酵母酿酒酵母中，端粒长度的维持涉及一个复杂的网络，因为在非必需基因缺失突变体组中已鉴定出超过280个端粒维持基因。作为补充，我们鉴定出另外29个端粒维持基因，这些基因以前被视为必需基因。在本研究中，我们报告了Sua5p在端粒复制中的新功能。上位性分析和端粒测序表明，sua5Δ细胞在传代早期显示出端粒逐渐缩短，且Sua5在端粒酶募集的下游起作用。此外，生化、结构和遗传学研究表明，Sua5p在体外通过其表面一个独特的DNA结合区域特异性结合单链端粒（ssTG）DNA，且DNA结合能力对其端粒功能至关重要。因此，Sua5p代表一种新型的ssTG DNA结合蛋白，并在体内正向调节端粒长度。
