Mandemaker Imke K, Vermeulen Wim, Marteijn Jurgen A
Department of Genetics; Erasmus Medical Centre; Rotterdam, the Netherlands.
Nucleus. 2014 May-Jun;5(3):203-10. doi: 10.4161/nucl.29085. Epub 2014 May 8.
During transcription, RNA polymerase may encounter DNA lesions, which causes stalling of transcription. To overcome the RNA polymerase blocking lesions, the transcribed strand is repaired by a dedicated repair mechanism, called transcription coupled nucleotide excision repair (TC-NER). After repair is completed, it is essential that transcription restarts. So far, the regulation and exact molecular mechanism of this transcriptional restart upon genotoxic damage has remained elusive. Recently, three different chromatin remodeling factors, HIRA, FACT, and Dot1L, were identified to stimulate transcription restart after DNA damage. These factors either incorporate new histones or establish specific chromatin marks that will gear up the chromatin to subsequently promote transcription recovery. This adds a new layer to the current model of chromatin remodeling necessary for repair and indicates that this specific form of transcription, i.e., the transcriptional restart upon DNA damage, needs specific chromatin remodeling events.
在转录过程中，RNA聚合酶可能会遇到DNA损伤，从而导致转录停滞。为了克服RNA聚合酶受阻的损伤，转录链通过一种专门的修复机制进行修复，称为转录偶联核苷酸切除修复（TC-NER）。修复完成后，转录重新启动至关重要。到目前为止，这种基因毒性损伤后转录重新启动的调控和确切分子机制仍然不清楚。最近，三种不同的染色质重塑因子HIRA、FACT和Dot1L被确定为在DNA损伤后刺激转录重新启动。这些因子要么整合新的组蛋白，要么建立特定的染色质标记，从而使染色质做好准备，随后促进转录恢复。这为当前修复所需的染色质重塑模型增添了新的层面，并表明这种特定形式的转录，即DNA损伤后的转录重新启动，需要特定的染色质重塑事件。
