...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The EMBO journal. >MST2 kinase suppresses rDNA transcription in response to DNA damage by phosphorylating nucleolar histone H2B
【24h】

MST2 kinase suppresses rDNA transcription in response to DNA damage by phosphorylating nucleolar histone H2B

机译：MST2激酶抑制rDNA转录应对DNA损伤通过磷酸化核仁的组蛋白H2B

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The heavily transcribed rDNA repeats that give rise to the ribosomal RNA are clustered in a unique chromatin structure, the nucleolus. Due to its highly repetitive nature and transcriptional activity, the nucleolus is considered a hotspot of genomic instability. Breaks in rDNA induce a transient transcriptional shut down to conserve energy and promote rDNA repair; however, how nucleolar chromatin is modified and impacts on rDNA repair is unknown. Here, we uncover that phosphorylation of serine 14 on histone H2B marks transcriptionally inactive nucleolar chromatin in response to DNA damage. We identified that the MST2 kinase localises at the nucleoli and targets phosphorylation of H2BS14p in an ATM-dependent manner. We show that establishment of H2BS14p is necessary for damage-induced rDNA transcriptional shut down and maintenance of genomic integrity. Ablation of MST2 kinase, or upstream activators, results in defective establishment of nucleolar H2BS14p, perturbed DNA damage repair, sensitisation to rDNA damage and increased cell lethality. We highlight the impact of chromatin regulation in the rDNA damage response and targeting of the nucleolus as an emerging cancer therapeutic approach.
机译：给的大量转录rDNA重复核糖体RNA都聚集在一个上升独特的染色质结构,核仁。其高度重复性质和转录活动,核仁被认为是一个热点基因组不稳定性。瞬态转录关闭来保护能源和促进rDNA修理;核仁的染色质的修改和影响rDNA修复是未知的。在组蛋白磷酸化的丝氨酸14 H2B的痕迹转录活性核仁的染色质应对DNA损伤。MST2激酶在核仁定位和目标的磷酸化H2BS14p ATM-dependent的方式。必要的损害rDNA转录关闭和维持基因组的完整性。消融MST2激酶或上游活化剂,结果建立核仁的缺陷H2BS14p,摄动DNA损伤修复,敏化作用rDNA伤害和增加细胞杀伤力。rDNA损伤反应和监管核仁的目标作为一个新兴的癌症治疗的方法。

著录项

相似文献

  • 外文文献
  • 中文文献
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