Abstract:
Cryptochromes (CRYs) are blue light (BL) photoreceptors to regulate a variety of physiological processes including DNA double-strand break (DSB) repair. SUPPRESSOR OF GAMMA RADIATION 1 (SOG1) acts as the central transcription factor of DNA damage response (DDR) to induce the transcription of downstream genes, including DSB repair-related genes BRCA1 and RAD51. Whether CRYs regulate DSB repair by directly modulating SOG1 is unknown. Here, we demonstrate that CRYs physically interact with SOG1. Disruption of CRYs and SOG1 leads to increased sensitivity to DSBs and reduced DSB repair-related genes\' expression under BL. Moreover, we found that CRY1 enhances SOG1\'s transcription activation of DSB repair-related gene BRCA1. These results suggest that the mechanism by which CRYs promote DSB repair involves positive regulation of SOG1\'s transcription of its target genes, which is likely mediated by CRYs-SOG1 interaction.
摘要:
隐色素(CRY)是蓝光(BL)光感受器,可调节多种生理过程,包括DNA双链断裂(DSB)修复。γ辐射抑制因子1(SOG1)作为DNA损伤反应(DDR)的中心转录因子,诱导下游基因转录,包括DSB修复相关基因BRCA1和RAD51。CRYs是否通过直接调节SOG1来调节DSB修复是未知的。这里,我们证明CRYs在物理上与SOG1相互作用。CRYs和SOG1的破坏导致对DSB的敏感性增加,并降低BL下DSB修复相关基因的表达。此外,我们发现CRY1增强SOG1对DSB修复相关基因BRCA1的转录激活。这些结果表明,CRYs促进DSB修复的机制涉及SOG1的靶基因转录的正向调节,这可能是由CRYs-SOG1相互作用介导的。