NASA Johnson Space Center, Houston, Texas 77058.
Curr Genomics. 2009 Jun;10(4):250-8. doi: 10.2174/138920209788488544.
Living organisms are constantly threatened by environmental DNA-damaging agents, including UV and ionizing radiation (IR). Repair of various forms of DNA damage caused by IR is normally thought to follow lesion-specific repair pathways with distinct enzymatic machinery. DNA double strand break is one of the most serious kinds of damage induced by IR, which is repaired through double strand break (DSB) repair mechanisms, including homologous recombination (HR) and non-homologous end joining (NHEJ). However, recent studies have presented increasing evidence that various DNA repair pathways are not separated, but well interlinked. It has been suggested that non-DSB repair mechanisms, such as Nucleotide Excision Repair (NER), Mismatch Repair (MMR) and cell cycle regulation, are highly involved in DSB repairs. These findings revealed previously unrecognized roles of various non-DSB repair genes and indicated that a successful DSB repair requires both DSB repair mechanisms and non-DSB repair systems. One of our recent studies found that suppressed expression of non-DSB repair genes, such as XPA, RPA and MLH1, influenced the yield of IR induced micronuclei formation and/or chromosome aberrations, suggesting that these genes are highly involved in DSB repair and DSB-related cell cycle arrest, which reveals new roles for these gene products in the DNA repair network. In this review, we summarize current progress on the function of non-DSB repair-related proteins, especially those that participate in NER and MMR pathways, and their influence on DSB repair. In addition, we present our developing view that the DSB repair mechanisms are more complex and are regulated by not only the well known HR/NHEJ pathways, but also a systematically coordinated cellular network.
生物体不断受到环境中 DNA 损伤因素的威胁，包括紫外线和电离辐射（IR）。通常认为，IR 引起的各种形式的 DNA 损伤的修复遵循特定损伤的修复途径，具有独特的酶机制。DNA 双链断裂是 IR 诱导的最严重的损伤之一，通过双链断裂（DSB）修复机制修复，包括同源重组（HR）和非同源末端连接（NHEJ）。然而，最近的研究越来越多地表明，各种 DNA 修复途径并不是相互独立的，而是密切相关的。有人提出，非 DSB 修复机制，如核苷酸切除修复（NER）、错配修复（MMR）和细胞周期调控，高度参与 DSB 修复。这些发现揭示了各种非 DSB 修复基因以前未被认识的作用，并表明成功的 DSB 修复需要 DSB 修复机制和非 DSB 修复系统。我们最近的一项研究发现，非 DSB 修复基因（如 XPA、RPA 和 MLH1）的表达受到抑制，会影响 IR 诱导的微核形成和/或染色体畸变的产量，这表明这些基因高度参与 DSB 修复和 DSB 相关的细胞周期停滞，这揭示了这些基因产物在 DNA 修复网络中的新作用。在这篇综述中，我们总结了非 DSB 修复相关蛋白，特别是参与 NER 和 MMR 途径的蛋白的功能的最新进展，以及它们对 DSB 修复的影响。此外，我们提出了我们正在发展的观点，即 DSB 修复机制更加复杂，不仅受 HR/NHEJ 途径的影响，还受到系统协调的细胞网络的调控。
