A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms.
A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms.
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DOI：
10.1038/nsmb.1974
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发表时间：
2011-02
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
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阻遏物激活蛋白1（RAP 1）是端粒中最保守的蛋白质。它参与保护裂殖酵母中的染色体末端，促进酿酒酵母中的基因沉默，而在乳酸克鲁维酵母中，它需要抑制端粒处的同源定向重组（HDR）。由于哺乳动物RAP 1需要TRF 2稳定表达，其在端粒功能中的作用仍然不清楚。为了了解RAP 1如何在端粒中发挥如此多样的功能，我们解决了来自多个生物体的RAP 1的C-末端RCT结构域的晶体或溶液结构，这些结构域与它们各自的蛋白质结合伴侣复合。我们的比较结构分析建立了RAP 1的RCT结构域作为进化上保守的蛋白质-蛋白质相互作用模块。在哺乳动物和裂殖酵母细胞中，该模块分别与TRF 2和Taz 1相互作用，将RAP 1靶向染色体末端以保护端粒末端。虽然RAP 1在裂变酵母端粒中抑制NHEJ，但在哺乳动物端粒中需要抑制HDR。相反，S.酿酒酵母RAP 1利用RCT结构域将Sir 3募集到端粒以介导基因沉默。总之，我们的研究结果表明，根据生物体，进化上保守的RAP 1 RCT基序在端粒中发挥着不同的功能作用。
Repressor activator protein 1 (RAP1) is the most highly conserved telomere protein. It is involved in protecting chromosome ends in fission yeast, promoting gene silencing in Saccharomyces cerevisiae while in Kluyveromyces lactis it is required to repress homology directed recombination (HDR) at telomeres. Since mammalian RAP1 requires TRF2 for stable expression, its role in telomere function has remained obscure. To understand how RAP1 plays such diverse functions at telomeres, we solved the crystal or solution structures of the C-terminal RCT domains of RAP1 from multiple organisms in complex with their respective protein-binding partners. Our comparative structural analysis establishes the RCT domain of RAP1 as an evolutionarily conserved protein-protein interaction module. In mammalian and fission yeast cells, this module interacts with TRF2 and Taz1, respectively, targeting RAP1 to chromosome ends for telomere end protection. While RAP1 repress NHEJ at fission yeast telomeres, at mammalian telomeres it is required to repress HDR. In contrast, S. cerevisiae RAP1 utilizes the RCT domain to recruit Sir3 to telomeres to mediate gene silencing. Together, our results reveal that depending on the organism, the evolutionarily conserved RAP1 RCT motif plays diverse functional roles at telomeres.
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影响因子：
2.6
作者：
Hentges, P;Van Driessche, B;Carr, AM
通讯作者：
Carr, AM
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
16
作者：
Bae, Nancy S.;Baumann, Peter
通讯作者：
Baumann, Peter
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A
影响因子：
2.7
作者：
Bailey, SM;Goodwin, EH;Cornforth, MN
通讯作者：
Cornforth, MN