A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint
A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint
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DOI：
10.1101/gad.1293805
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发表时间：
2005-11-01
影响因子：
10.5
通讯作者：
Weinert, T
中科院分区：
文献类型：
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作者：
Michelson, RJ;Rosenstein, S;Weinert, T
端粒是一种复杂的结构，用于保护染色体末端。在这里，我们提供的证据表明，在酿酒酵母端粒可能含有抗检查点活性，防止染色体末端信号细胞周期停滞。我们发现，端粒重复序列的内部束抑制相邻双链断裂（DSB）的DNA损伤检查点信号传导;正常DSB的细胞周期停滞持续8- 1 - 2小时，而端粒重复序列相邻的DSB仅持续1-2小时。缩短或缩短的停滞不是DNA修复的结果，也不是单链DNA数量减少的结果，也不是适应的结果。这种端粒重复相关的抗检查点活性的分子身份是未知的，尽管它不依赖于端粒酶或端粒近端基因沉默。抗检查点可能会抑制ATR酵母直系同源物Mec 1，因为Rad 9和Rad 53在缩短的停滞期间变得去磷酸化和失活。抗检查点的作用区域;它抑制信号从DNA断裂到0.6 kb远离端粒重复，但不是从一个单独的染色体上存在的DSB。我们提出，在端粒重复序列附近形成DSB后，成熟的端粒会在1-2小时内形成，然后端粒含有抑制附近DNA断裂的检查点信号的蛋白质。
Telomeres are complex structures that serve to protect chromosome ends. Here we provide evidence that in Saccharomyces cerevisiae telomeres may contain an anticheckpoint activity that prevents chromosome ends from signaling cell cycle arrest. We found that an internal tract of telomeric repeats inhibited DNA damage checkpoint signaling from adjacent double-strand breaks (DSBs); cell cycle arrest lasted 8-12 h from a normal DSB, whereas it lasted only 1-2 h from a DSB adjacent to a telomeric repeat. The shortened or abridged arrest was not the result of DNA repair, nor reduced amounts of single-stranded DNA, nor of adaptation. The molecular identity of this telomere repeat-associated anticheckpoint activity is unknown, though it is not dependent upon telomerase or telomere-proximal gene silencing. The anticheckpoint may inhibit the ATR yeast ortholog Mec1 because Rad9 and Rad53 became dephosphorylated and inactivated during the abridged arrest. The anticheckpoint acts regionally; it inhibited signaling from DNA breaks up to 0.6 kb away from the telomeric repeat but not from a DSB present on a separate chromosome. We propose that after formation of the DSB near the telomeric repeat, a mature telomere forms in 1-2 h, and the telomere then contains proteins that inhibit checkpoint signaling from nearby DNA breaks.