UV-Induced Association of the CSB Remodeling Protein with Chromatin Requires ATP-Dependent Relief of N-Terminal Autorepression
UV-Induced Association of the CSB Remodeling Protein with Chromatin Requires ATP-Dependent Relief of N-Terminal Autorepression
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DOI：
10.1016/j.molcel.2009.10.027
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发表时间：
2010-01-29
期刊：
影响因子：
16
通讯作者：
Fan, Hua-Ying
中科院分区：
文献类型：
--
作者：
Lake, Robert J.;Geyko, Anastasia;Fan, Hua-Ying
ATP依赖性染色质重塑因子CSB是转录偶联DNA修复所必需的，CSB的突变导致Cockayne综合征。在这里，我们研究了招聘的CSB染色质紫外线（UV）照射后，并揭示了一个监管机制，确保这种重塑与染色质的特定关联。我们证明，ATP水解GSB是必不可少的稳定的CSB染色质协会紫外线照射后，这种协会的缺陷的基础上的某些形式的Cockayne综合征。我们还表明，在正常细胞生长过程中，CSB的N-末端区域负调控染色质缔合。感兴趣的是，在负调控区的情况下，ATP水解成为染色质缔合的抑制剂，表明CSB使用来自ATP水解的能量来克服其N-末端区域施加的抑制作用。总之，我们的研究结果表明，招聘的CSB病变停滞的转录是一个ATP依赖的过程，并涉及一个总的构象变化的CSB。
The ATP-dependent chromatin remodeler CSB is essential for transcription-coupled DNA repair, and mutations in CSB lead to Cockayne syndrome. Here, we examined the recruitment of CSB to chromatin after ultraviolet (UV) irradiation and uncovered a regulatory mechanism that ensures the specific association of this remodeler with chromatin. We demonstrate that ATP hydrolysis by GSB is essential for stable CSB-chromatin association after UV irradiation and that defects in this association underlie some forms of Cockayne syndrome. We also show that the N-terminal region of CSB negatively regulates chromatin association during normal cell growth. Of interest, in the absence of the negative regulatory region, ATP hydrolysis becomes dispensable for chromatin association, indicating that CSB uses energy from ATP hydrolysis to overcome the inhibitory effect imposed by its N-terminal region. Together, our results suggest that the recruitment of CSB to lesion-stalled transcription is an ATP-dependent process and involves a gross conformational change of CSB.