...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Fission Yeast Rad17 Associates with Chromatin in Response to Aberrant Genomic Structures
【24h】

Fission Yeast Rad17 Associates with Chromatin in Response to Aberrant Genomic Structures

机译：裂变酵母Rad17与染色质联合应对异常的基因组结构。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Fission yeast checkpoint protein Rad17 is required for the DNA integrity checkpoint responses. A fraction of Rad17 is chromatin bound independent of the other checkpoint proteins throughout the cell cycle. Here we show that in response to DNA damage induced by either methyl methanesulfonate treatment or ionizing radiation, increased levels of Rad17 bind to chromatin. Following S-phase stall induced by hydroxyurea or a cdc22 mutation, the chromatin-bound Rad17 progressively dissociates from the chromatin. After S-phase arrest by hydroxyurea in cds1Δ or rad3Δ cells or by replication mutants, Rad17 remains chromatin bound. Rad17 is able to complex in vivo with an Rfc small subunit, Rfc2, but not with Rfc1. Furthermore, cells with rfc1Δ are checkpoint proficient, suggesting that Rfc1 does not have a role in checkpoint function. A checkpoint-defective mutant protein, Rad17(K118E), which has similar nuclear localization to that of the wild type, is unable to bind ATP and has reduced ability in chromatin binding. Mutant Rad17(K118E) protein also has reduced ability to complex with Rfc2, suggesting that Lys118 of Rad17 plays a role in Rad17-Rfc small-subunit complex formation and chromatin association. However, in therad17.K118E mutant cells, Cds1 can be activated by hydroxyurea. Together, these results suggest that Rad17 binds to chromatin in response to an aberrant genomic structure generated from DNA damage, replication mutant arrest, or hydroxyurea arrest in the absence of Cds1. Rad17 is not required to bind chromatin when genomic structures are protected by hydroxyurea-activated Cds1. The possible checkpoint events induced by chromatin-bound Rad17 are discussed.
机译：裂变酵母检查点蛋白Rad17是DNA完整性检查点响应所必需的。在整个细胞周期中，Rad17的一部分与染色质结合，而与其他检查点蛋白无关。在这里，我们表明，响应由甲磺酸甲酯处理或电离辐射引起的DNA损伤，Rad17的水平增加与染色质结合。由羟基脲或 cdc22 突变引起的S期停滞后，与染色质结合的Rad17逐渐从染色质上解离。 S期被 cds1 Δ或 rad3 Δ细胞中的羟基脲或复制突变体阻滞后，Rad17仍与染色质结合。 Rad17能够与Rfc小亚基Rfc2在体内复合，但不能与Rfc1复杂。此外，具有 rfc1 Δ的细胞具有检查点能力，这表明Rfc1在检查点功能中不起作用。检查点缺陷型突变蛋白Rad17（K118E）的核定位与野生型相似，无法结合ATP，并且染色质结合能力降低。 Rad17（K118E）突变蛋白与Rfc2的复合能力也降低，这表明Rad17的Lys 118 在Rad17-Rfc小亚基复合物的形成和染色质缔合中起作用。然而，在 rad17.K118E 突变细胞中，Cds1可以被羟基脲激活。总之，这些结果表明，在没有Cds1的情况下，Rad17响应于由DNA损伤，复制突变体停滞或羟基脲停滞而产生的异常基因组结构，与染色质结合。当基因组结构受羟基脲激活的Cds1保护时，Rad17不需要结合染色质。讨论了由染色质结合的Rad17诱导的可能的检查点事件。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号