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Regulation of telomere length and function by a Myb-domain protein in fission yeast

机译:裂变酵母中Myb域蛋白调节端粒的长度和功能

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Telomeres, the specialized nucleoprotein structures that comprise the ends of eukaryotic chromosomes, are essential for complete replication, and regulation of their length has been a focus of research on tumorigenesis. In the budding yeast Saccharomyces cerevisiae, the protein Rap1p binds to telomeric DNA and functions in the regulation of telomere length. A human telomere protein, hTRF (human TTAGGG repeat factor) binds the telomere sequence in vitro and localizes to telomeres cytologically, 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 Schizosaccharomyces 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, or may protect against activation of telomerase-independent pathways of telomere elongation.
机译:端粒是构成真核染色体末端的特殊核蛋白结构,对于完全复制至关重要,其长度调节一直是肿瘤发生研究的重点。在出芽的酿酒酵母中,Rap1p蛋白与端粒DNA结合并在端粒长度的调节中起作用。人端粒蛋白hTRF(人TTAGGG重复因子)在体外结合端粒序列,并在细胞学上定位于端粒,但其功能尚不清楚。在这里,我们使用遗传筛选来鉴定裂变酵母Taz1p(与端粒裂殖酵母相关的端粒)中的端粒蛋白,该蛋白与hTRF的Myb原癌基因DNA结合结构域具有同源性。 taz1 +基因的破坏或缺失导致端粒长度大量增加。 Taz1p是抑制邻近端粒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,端粒酶的负调节剂,或者可以防止端粒酶非依赖性的端粒延长途径的激活。

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