Regulation of telomere length and function by a Myb-domain protein in fission yeast
Regulation of telomere length and function by a Myb-domain protein in fission yeast
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DOI：
10.1038/385744a0
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发表时间：
1997-02-20
期刊：
影响因子：
64.8
通讯作者：
Cech, TR
中科院分区：
文献类型：
--
作者：
Cooper, JP;Nimmo, ER;Cech, TR
端粒是一种特殊的核蛋白结构，包含真核细胞染色体的末端（1，2），对于完整复制至关重要（3-5），调节其长度一直是肿瘤发生研究的焦点（6-8）。在芽殖酵母酿酒酵母中，蛋白质Rap 1 p与端粒DNA结合，并在调节端粒长度中发挥作用（9-12）。人端粒蛋白hTRF（人TTAGGG重复因子）在体外结合端粒序列（13）并在细胞学上定位于端粒（14），但其功能尚不清楚。在这里，我们使用遗传筛选，以确定一个端粒蛋白在裂殖酵母，Taz 1 p（端粒相关的裂殖酵母），共享同源性的Myb原癌基因DNA结合域与hTRF。taz 1（+）基因的破坏或缺失会导致端粒长度的大量增加。Taz 1 p是抑制端粒邻近基因表达和正常减数分裂或孢子形成所必需的。它可能是端粒复制酶端粒酶（1，3）的负调节剂，或可能防止端粒延长的端粒酶非依赖性途径的激活（8）。
Telomeres, the specialized nucleoprotein structures that comprise the ends of eukaryotic chromosomes(1,2), are essential for complete replication(3-5), and regulation of their length has been a focus of research on tumorigenesis(6-8). In the budding yeast Saccharomyces cerevisiae, the protein Rap1p binds to telomeric DNA and functions in the regulation of telomere length(9-12). A human telomere protein, hTRF (human TTAGGG repeat factor) binds the telomere sequence in vitro(13) and localizes to telomeres cytologically(14), but its functions are not yet known. Here we use a genetic screen to identify a telomere protein in fission yeast, Taz1p (telomere-associated in Schizosaccharomycesrces pombe), that shares homology to the Myb proto-oncogene DNA-binding domain with hTRF. Disruption or deletion of the taz1(+) gene causes a massive increase in telomere length. Taz1p is required for the repression of telomere-adjacent gene expression and for normal meiosis or sporulation. It may be a negative regulator of the telomere-replicating enzyme, telomerase(1,3), or may protect against activation of telomerase-independent pathways of telomere elongation(8).