DNA damage repair systems are critical for genomic integrity. However, they must be coordinated with DNA replication and cell division to ensure accurate genomic transmission. In most bacteria, this coordination is mediated by the SOS response through LexA, which triggers a halt in cell division until repair is completed. Recently, an SOS-independent damage response system was revealed in Caulobacter crescentus. This pathway is controlled by the transcription activator, DriD, but how DriD senses and signals DNA damage is unknown. To address this question, we performed biochemical, cellular, and structural studies. We show that DriD binds a specific promoter DNA site via its N-terminal HTH domain to activate transcription of genes, including the cell division inhibitor didA. A structure of the C-terminal portion of DriD revealed a WYL motif domain linked to a WCX dimerization domain. Strikingly, we found that DriD binds ssDNA between the WYL and WCX domains. Comparison of apo and ssDNA-bound DriD structures reveals that ssDNA binding orders and orients the DriD domains, indicating a mechanism for ssDNA-mediated operator DNA binding activation. Biochemical and in vivo studies support the structural model. Our data thus reveal the molecular mechanism underpinning an SOS-independent DNA damage repair pathway.

中文翻译：

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ssDNA 是 C. crescentus SOS 独立 DNA 损伤反应转录激活剂 DriD 的变构调节剂


DNA 损伤修复系统对于基因组完整性至关重要。然而，它们必须与 DNA 复制和细胞分裂相协调，以确保基因组的准确传递。在大多数细菌中，这种协调是由 LexA 的 SOS 反应介导的，它会触发细胞分裂停止，直到修复完成。最近，新月柄杆菌中发现了一个独立于 SOS 的损伤反应系统。该通路由转录激活剂 DriD 控制，但 DriD 如何感知 DNA 损伤并发出信号尚不清楚。为了解决这个问题，我们进行了生化、细胞和结构研究。我们发现 DriD 通过其 N 端 HTH 结构域结合特定的启动子 DNA 位点，以激活基因转录，包括细胞分裂抑制剂didA 。 DriD C 端部分的结构揭示了与 WCX 二聚化结构域相连的 WYL 基序结构域。引人注目的是，我们发现 DriD 结合 WYL 和 WCX 结构域之间的单链 DNA。 apo 和 ssDNA 结合的 DriD 结构的比较揭示了 ssDNA 结合对 DriD 结构域进行排序和定向，表明了 ssDNA 介导的操纵基因 DNA 结合激活的机制。生化和体内研究支持结构模型。因此，我们的数据揭示了独立​​于 SOS 的 DNA 损伤修复途径的分子机制。