Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation.
Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation.
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DOI：
10.1093/nar/gkw807
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发表时间：
2016-11-16
影响因子：
14.9
通讯作者：
Shippen DE
中科院分区：
文献类型：
--
作者：
Arora A;Beilstein MA;Shippen DE
端粒保护（POT 1）结合染色体末端，通过两个寡核苷酸/寡糖结合折叠（OB-折叠）识别单链端粒DNA。拟南芥POT 1a和POT 1b旁系同源物是非典型的：它们不表现出端粒DNA结合，并且它们在调节端粒酶活性方面具有相反的作用。AtPOT 1a刺激典型端粒酶的重复添加持续合成能力，而AtPOT 1b与抑制端粒酶活性的调控lncRNA相互作用。在这里，我们表明POT 1a的OB 1（而不是POT 1b）对端粒DNA具有内在的亲和力。DNA结合依赖于高度保守的Phe残基（F65），其在人POT 1中直接接触端粒DNA。POT 1aOB 1的F65 A突变破坏了DNA结合，降低了端粒酶重复序列添加的持续性。相反，AtPOT 1b和其他POT 1b同源物从紫云英科和它的姐妹家庭，Cleomaceae，天然携带非芳香族氨基酸在这个位置。通过将瓦尔（V63）与Phe交换，AtPOT 1bOB 1获得了结合端粒DNA和刺激端粒酶重复添加持续合成能力的能力。我们的结论是，在DNA结合的情况下，在一个单一的氨基酸位置的变化促进分化的AtPOT 1b paradox从祖先POT 1蛋白。
Protection of telomeres (POT1) binds chromosome ends, recognizing single-strand telomeric DNA via two oligonucleotide/oligosaccharide binding folds (OB-folds). The Arabidopsis thaliana POT1a and POT1b paralogs are atypical: they do not exhibit telomeric DNA binding, and they have opposing roles in regulating telomerase activity. AtPOT1a stimulates repeat addition processivity of the canonical telomerase enzyme, while AtPOT1b interacts with a regulatory lncRNA that represses telomerase activity. Here, we show that OB1 of POT1a, but not POT1b, has an intrinsic affinity for telomeric DNA. DNA binding was dependent upon a highly conserved Phe residue (F65) that in human POT1 directly contacts telomeric DNA. F65A mutation of POT1aOB1 abolished DNA binding and diminished telomerase repeat addition processivity. Conversely, AtPOT1b and other POT1b homologs from Brassicaceae and its sister family, Cleomaceae, naturally bear a non-aromatic amino acid at this position. By swapping Val (V63) with Phe, AtPOT1bOB1 gained the capacity to bind telomeric DNA and to stimulate telomerase repeat addition processivity. We conclude that, in the context of DNA binding, variation at a single amino acid position promotes divergence of the AtPOT1b paralog from the ancestral POT1 protein.
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影响因子：
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