Involvement of Hus1 in the chain elongation step of DNA replication after exposure to camptothecin or ionizing radiation (Retracted article. See vol. 48, pg. 3396, 2020)
Involvement of Hus1 in the chain elongation step of DNA replication after exposure to camptothecin or ionizing radiation (Retracted article. See vol. 48, pg. 3396, 2020)
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DOI：
10.1093/nar/gkh243
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Wang, Y
中科院分区：
文献类型：
--
作者：
Wang, X;Guan, J;Wang, Y
DNA损伤诱导的S阶段(S)检查点包括对复制子起始和链延长的抑制。控制这两个过程的确切机制仍不清楚。在这项研究中，我们发现HUS1缺失的小鼠细胞在暴露于DNA链断裂诱导剂如喜树碱(大于或等于1.0微米)或电离辐射(IR)(大于或等于15GY)后，存在受损的S检查点。依赖于HUS1的S检查点参与了细胞对CPT的抗性。CPT或IR对HUS1基因缺陷细胞的S检查点的损伤主要反映了DNA复制的链延长步骤，并与减少增殖细胞核抗原从DNA复制区解离有关。尽管HUS1是细胞暴露于CPT或IR后RAD9磷酸化所必需的，但HUS1缺陷的细胞在出现检查点缺陷的剂量下显示出ATR/CHK1和ATMK的正常激活，这表明HUS1不是CPT或IR诱导的S检查点激活这些通路的传感器系统的组成部分。
DNA damage-induced S phase (S) checkpoint includes inhibition of both replicon initiation and chain elongation. The precise mechanism for controlling the two processes remains unclear. In this study, we showed that Hus1-deficient mouse cells had an impaired S checkpoint after exposure to DNA strand break-inducing agents such as camptothecin (CPT) (greater than or equal to1.0 muM), or ionizing radiation (IR) (greater than or equal to15 Gy). The Hus1-dependent S checkpoint contributes to cell resistance to CPT. This impaired S checkpoint induced by CPT or IR in Hus1-deficient cells reflected mainly the chain elongation step of DNA replication and was correlated with the reduction of dissociation of PCNA from DNA replication foci. Although Hus1 is required for Rad9 phosphorylation following exposure of cells to CPT or IR, Hus1-deficient cells showed normal activation of ATR/CHK1 and ATM kinases at doses where the checkpoint defects were manifested, suggesting that Hus1 is not a component of the sensor system for activating these pathways in S checkpoint induced by CPT or IR.