Jung Kwang-Woo, Jung Jong-Hyun, Park Ha-Young
Radiation Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-Si 56212, Jeollabuk-Do, Korea.
Department of Radiation Science and Technology, University of Science and Technology, Daejeon 34113, Korea.
J Fungi (Basel). 2021 Jul 16;7(7):566. doi: 10.3390/jof7070566.
DNA double-strand breaks (DSBs) are the most deleterious type of DNA lesions because they cause loss of genetic information if not properly repaired. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ) are required for DSB repair. However, the relationship of HR and NHEJ in DNA damage stress is unknown in the radiation-resistant fungus . In this study, we found that the expression levels of HR- and NHEJ-related genes were highly induced in a Rad53-Bdr1 pathway-dependent manner under genotoxic stress. Deletion of , which is one of the main components in the HR, resulted in growth under diverse types of DNA damage stress, whereas perturbations of and , which belong to the NHEJ system, did not affect the genotoxic stresses except when bleomycin was used for treatment. Furthermore, deletion of both and / renders cells susceptible to oxidative stress. Notably, we found that deletion of induced a hypermutator phenotype in the fluctuation assay. In contrast to the fluctuation assay, perturbation of or induced rapid microevolution similar to that induced by the deletion of . Collectively, Rad51-mediated HR and Ku70/Ku80-mediated NHEJ regulate the DNA damage response and maintain genome stability.
DNA双链断裂（DSBs）是最具危害性的DNA损伤类型，因为如果不进行适当修复，它们会导致遗传信息丢失。在真核生物中，DNA双链断裂修复需要同源重组（HR）和非同源末端连接（NHEJ）。然而，在抗辐射真菌中，HR和NHEJ在DNA损伤应激中的关系尚不清楚。在本研究中，我们发现，在遗传毒性应激下，HR和NHEJ相关基因的表达水平以Rad53-Bdr1途径依赖性方式被高度诱导。HR的主要成分之一Rad51的缺失导致细胞在多种类型的DNA损伤应激下生长受影响，而属于NHEJ系统的Ku70和Ku80的扰动，除了使用博来霉素处理外，不影响遗传毒性应激。此外，Rad51和Ku70/Ku80两者都缺失使细胞对氧化应激敏感。值得注意的是，我们发现在波动试验中Rad51的缺失诱导了高突变体表型。与波动试验相反，Ku70或Ku80的扰动诱导了类似于Rad51缺失所诱导的快速微进化。总之，Rad51介导的HR和Ku70/Ku80介导的NHEJ调节DNA损伤反应并维持基因组稳定性。
