ATR regulates fragile site stability
ATR regulates fragile site stability
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DOI：
10.1016/s0092-8674(02)01113-3
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发表时间：
2002-12-13
期刊：
影响因子：
64.5
通讯作者：
Glover, TW
中科院分区：
文献类型：
--
作者：
Casper, AM;Nghiem, P;Glover, TW
部分抑制DNA复制的条件会诱导常见位点的表达。这些位点在中期染色体上形成间隙和断裂，并在许多肿瘤中被删除和重新排列。然而，脆弱的位点表达的机制是难以捉摸的。我们证明复制检查点激酶ATR而不是ATM对于维持脆弱的现场稳定性至关重要。 ATR缺乏会导致脆弱的位点表达，而无需添加复制抑制剂。因此，我们建议脆弱的位点是由于失速的叉子而产生的未复制的染色体区域。这些发现对于理解脆弱位点不稳定性的机制和哺乳动物细胞中停滞复制的后果具有重要意义。
Conditions that partially inhibit DNA replication induce expression of common fragile sites. These sites form gaps and breaks on metaphase chromosomes and are deleted and rearranged in many tumors. Yet, the mechanism of fragile site expression has been elusive. We demonstrate that the replication checkpoint kinase ATR, but not ATM, is critical for maintenance of fragile site stability. ATR deficiency results in fragile site expression with and without addition of replication inhibitors. Thus, we propose that fragile sites are unreplicated chromosomal regions resulting from stalled forks that escape the ATR replication checkpoint. These findings have important implications for understanding both the mechanism of fragile site instability and the consequences of stalled replication in mammalian cells.