RPA facilitates telomerase activity at chromosome ends in budding and fission yeasts
RPA facilitates telomerase activity at chromosome ends in budding and fission yeasts
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DOI：
10.1038/emboj.2012.40
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发表时间：
2012-04-18
期刊：
影响因子：
11.4
通讯作者：
Geli, Vincent
中科院分区：
文献类型：
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作者：
Luciano, Pierre;Coulon, Stephane;Geli, Vincent
在酿酒酵母中，端粒酶复合物结合到染色体末端，并通过与复制叉的进展偶联的过程在晚期S期被激活。在这里，我们表明，单链DNA结合蛋白RPA（复制蛋白A）结合到两个女儿端粒端粒在端粒复制过程中，但只有其结合到前导链端粒依赖于Mre 11/Rad 50/Xrs 2（MRX）复合物。我们进一步证明RPA特异性地与yKu、Cdc 13和端粒酶共沉淀。RPA与端粒酶的相互作用似乎由yKu和端粒酶亚基Est 1介导。此外，影响与yKu和端粒酶的相互作用的Rfa 1中的突变减少了rif 1 Delta，rif 2 Delta双突变体的端粒长度的急剧增加。最后，我们表明RPA/端粒酶协会和功能是保守的裂殖酵母粟酒裂殖酵母。我们的研究结果表明，在这两种酵母，RPA直接促进染色体末端的端粒酶活性。The EMBO Journal（2012）31，2034-2046. doi：10.1038/daj.2012.40;在线发表2012年2月21日主题分类：基因组稳定性和动力学
In Saccharomyces cerevisiae, the telomerase complex binds to chromosome ends and is activated in late S-phase through a process coupled to the progression of the replication fork. Here, we show that the single-stranded DNA-binding protein RPA (replication protein A) binds to the two daughter telomeres during telomere replication but only its binding to the leading-strand telomere depends on the Mre11/Rad50/Xrs2 (MRX) complex. We further demonstrate that RPA specifically co-precipitates with yKu, Cdc13 and telomerase. The interaction of RPA with telomerase appears to be mediated by both yKu and the telomerase subunit Est1. Moreover, a mutation in Rfa1 that affects both the interaction with yKu and telomerase reduces the dramatic increase in telomere length of a rif1 Delta, rif2 Delta double mutant. Finally, we show that the RPA/telomerase association and function are conserved in Schizosaccharomyces pombe. Our results indicate that in both yeasts, RPA directly facilitates telomerase activity at chromosome ends. The EMBO Journal (2012) 31, 2034-2046. doi: 10.1038/emboj.2012.40; Published online 21 February 2012 Subject Categories: genome stability & dynamics