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首页> 外文期刊>Molecular and Cellular Biology >Chk1-Dependent S-M Checkpoint Delay in Vertebrate Cells Is Linked to Maintenance of Viable Replication Structures
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Chk1-Dependent S-M Checkpoint Delay in Vertebrate Cells Is Linked to Maintenance of Viable Replication Structures

机译：Chk1依赖于脊椎动物细胞中的S-M检查点延迟链接到可行的复制结构的维护。

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We investigated mitotic delay during replication arrest (the S-M checkpoint) in DT40 B-lymphoma cells deficient in the Chk1 or Chk2 kinase. We show here that cells lacking Chk1, but not those lacking Chk2, enter mitosis with incompletely replicated DNA when DNA synthesis is blocked, but only after an initial delay. This initial delay persists when S-M checkpoint failure is induced in Chk2?/? cells with the Chk1 inhibitor UCN-01, indicating that it does not depend on Chk1 or Chk2 activity. Surprisingly, dephosphorylation of tyrosine 15 did not accompany Cdc2 activation during premature entry to mitosis in Chk1?/? cells, although mitotic phosphorylation of cyclin B2 did occur. Previous studies have shown that Chk1 is required to stabilize stalled replication forks during replication arrest, and strikingly, premature mitosis occurs only in Chk1-deficient cells which have lost the capacity to synthesize DNA as a result of progressive replication fork inactivation. These results suggest that Chk1 maintains the S-M checkpoint indirectly by preserving the viability of replication structures and that it is the continued presence of such structures, rather than the activation of Chk1 per se, which delays mitosis until DNA replication is complete.
机译：我们调查了Chk1或Chk2激酶缺陷的DT40 B淋巴瘤细胞在复制停滞（S-M检查点）期间的有丝分裂延迟。我们在此处显示，当DNA合成受阻时（但仅在最初延迟之后），缺少Chk1的细胞但不缺少缺少Chk2的细胞进入具有不完全复制的DNA的有丝分裂。当使用Chk1抑制剂UCN-01在Chk2 ？/？细胞中诱导S-M检查点失败时，这种初始延迟仍然存在，这表明它不依赖于Chk1或Chk2活性。出乎意料的是，尽管细胞周期蛋白B 2 发生了有丝分裂磷酸化，但Chk1 ？/？细胞中过早进入有丝分裂过程中，酪氨酸15的去磷酸化并未伴随Cdc2活化。先前的研究表明，Chk1是稳定复制停滞过程中停滞的复制叉所必需的，而且引人注目的是，过早有丝分裂只发生在Chk1缺陷型细胞中，这些细胞由于进行性复制叉的失活而失去了合成DNA的能力。这些结果表明，Chk1通过保留复制结构的生存能力间接维持S-M检查点，而正是这种结构的持续存在，而不是Chk1本身的激活，这延迟了有丝分裂直至DNA复制完成。

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