RPA and POT1 Friends or foes at telomeres?
RPA and POT1 Friends or foes at telomeres?
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DOI：
10.4161/cc.11.4.19061
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发表时间：
2012-02-15
期刊：
影响因子：
4.3
通讯作者：
Zou, Lee
中科院分区：
文献类型：
--
作者：
Flynn, Rachel Litman;Chang, Sandy;Zou, Lee
循环细胞中端粒的维持依赖于 DNA 复制和蛋白质复合物庇护蛋白的加帽。两种单链 DNA (ssDNA) 结合蛋白、复制蛋白 A (RPA) 和端粒保护 1 (POT1) 分别在 DNA 复制和端粒加帽中发挥关键作用。 RPA 以非序列特异性方式与 ssDNA 结合，而 POT1 特异性识别单链 TTAGGG 端粒重复序列。 POT1 的缺失导致 RPA 在端粒处异常积累，并激活共济失调性毛细血管扩张和 Rad3 相关激酶 (ATR) 介导的检查点反应，表明 POT1 拮抗 RPA 与端粒 ssDNA 的结合。端粒维持对 POT1 和 RPA 的需求以及这两种蛋白质之间的拮抗作用提出了一个重要问题：它们如何在端粒 ssDNA 上协同发挥作用。最近的研究提出了两个有趣的模型来解释 POT1 和 RPA 在端粒上的调节。在这里，我们讨论这些模型如何帮助揭示细胞周期中 POT1 和 RPA 之间的协调和拮抗作用。
Telomere maintenance in cycling cells relies on both DNA replication and capping by the protein complex shelterin. Two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomere 1 (POT1) play critical roles in DNA replication and telomere capping, respectively. While RPA binds to ssDNA in a non-sequence-specific manner, POT1 specifically recognizes single-stranded TTAGGG telomeric repeats. Loss of POT1 leads to aberrant accumulation of RPA at telomeres and activation of the ataxia telangiectasia and Rad3-related kinase (ATR)-mediated checkpoint response, suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. The requirement for both POT1 and RPA in telomere maintenance and the antagonism between the two proteins raises the important question of how they function in concert on telomeric ssDNA. Two interesting models were proposed by recent studies to explain the regulation of POT1 and RPA at telomeres. Here, we discuss how these models help unravel the coordination, and also the antagonism, between POT1 and RPA during the cell cycle.