Structure of transcribed chromatin is a sensor of DNA damage.
Structure of transcribed chromatin is a sensor of DNA damage.
复制标题
转录染色质的结构是 DNA 损伤的传感器。
DOI：
10.1126/sciadv.1500021
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发表时间：
2015
期刊：
影响因子：
13.6
通讯作者：
Studitsky,VasilyM
中科院分区：
文献类型：
--
作者：
Pestov,NikolayA;Gerasimova,NadezhdaS;Kulaeva,OlgaI;Studitsky,VasilyM
早期发现和修复受损的DNA对细胞功能和生存至关重要。尽管多个细胞系统参与了单链DNA断裂（SSB）的修复，但仍不清楚如何检测染色质中组织的DNA非模板链（NT-SSB）中存在的SSB。研究了NT-SSBs对RNA聚合酶II通过染色质转录的影响。NT-SSBs位于核小体DNA的启动子近端区域，隐藏在核小体结构中，可以诱导断裂下游的RNA聚合酶几乎定量的停滞，而更多的启动子远端SSBs适度地促进转录。核小体DNA上的阻滞位点的位置表明，小的核小体内DNA环的形成导致阻滞。该机制可能涉及NT-SSB通过染色质在转录过程中积累的不受约束的DNA超螺旋的缓解。这些数据表明存在一种新的染色质特异性机制，允许通过转录酶检测NT-SSB。
Early detection and repair of damaged DNA is essential for cell functioning and survival. Although multiple cellular systems are involved in the repair of single-strand DNA breaks (SSBs), it remains unknown how SSBs present in the nontemplate strand (NT-SSBs) of DNA organized in chromatin are detected. The effect of NT-SSBs on transcription through chromatin by RNA polymerase II was studied. NT-SSBs localized in the promoter-proximal region of nucleosomal DNA and hidden in the nucleosome structure can induce a nearly quantitative arrest of RNA polymerase downstream of the break, whereas more promoter-distal SSBs moderately facilitate transcription. The location of the arrest sites on nucleosomal DNA suggests that formation of small intranucleosomal DNA loops causes the arrest. This mechanism likely involves relief of unconstrained DNA supercoiling accumulated during transcription through chromatin by NT-SSBs. These data suggest the existence of a novel chromatin-specific mechanism that allows the detection of NT-SSBs by the transcribing enzyme.