Pot1 and cell cycle progression cooperate in telomere length regulation
Pot1 and cell cycle progression cooperate in telomere length regulation
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DOI：
10.1038/nsmb1331
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发表时间：
2008-01-01
影响因子：
16.8
通讯作者：
Price, Carolyn M.
中科院分区：
文献类型：
--
作者：
Churikov, Dmitri;Price, Carolyn M.
脊椎动物端粒蛋白Pot1的去除导致DNA损伤反应和细胞周期停滞。在这里，我们表明，鸡Pot1的损失导致Chk1激活，和Chk1信号的抑制防止细胞周期停滞。然而，在ATM被破坏后仍然会发生停滞，ATM编码另一种DNA损伤反应蛋白。这些结果表明，Pot1需要防止由另一种这样的蛋白质ATR介导的端粒检查点，该蛋白质ATR最有可能由G-突出端触发。我们还表明，Pot1的去除导致异常快速的端粒生长后，逮捕在后期S/G2的细胞周期。然而，释放阻滞减缓端粒生长和G-突出端延长。因此，Pot1似乎通过与端粒的直接相互作用和防止细胞周期中的晚期S/G2延迟来调节端粒长度和G-突出端加工。我们的研究结果表明，细胞周期进程是端粒长度调节的重要组成部分。
Removal of the vertebrate telomere protein Pot1 results in a DNA damage response and cell cycle arrest. Here we show that loss of chicken Pot1 causes Chk1 activation, and inhibition of Chk1 signaling prevents the cell cycle arrest. However, arrest still occurs after disruption of ATM, which encodes another DNA damage response protein. These results indicate that Pot1 is required to prevent a telomere checkpoint mediated by another such protein, ATR, that is most likely triggered by the G-overhang. We also show that removal of Pot1 causes exceptionally rapid telomere growth upon arrest in late S/G2 of the cell cycle. However, release of the arrest slows both telomere growth and G-overhang elongation. Thus, Pot1 seems to regulate telomere length and G-overhang processing both through direct interaction with the telomere and by preventing a late S/G2 delay in the cell cycle. Our results reveal that cell cycle progression is an important component of telomere length regulation.