Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
Curr Genet. 2020 Feb;66(1):1-6. doi: 10.1007/s00294-019-01015-4. Epub 2019 Jul 18.
DNA double-strand breaks (DSBs) must be rejoined properly to prevent the occurrence of serious genomic rearrangements associated with many human diseases. Non-homologous end joining (NHEJ) is a DSB repair mechanism known to protect genomic integrity that is also implicated in creating genomic translocations, inversions, deletions, and insertions. We recently investigated the impact of the pre-damage spatial proximity of DSB-bearing loci on the frequency of trans repair by NHEJ and surprisingly found no correlation between them. In this review, we consider various models that might account for these unexpected results. While DSB movement is necessary to explain our findings, many questions remain about the nature and timing of that motion.
DNA 双链断裂 (DSB) 必须正确连接,以防止与许多人类疾病相关的严重基因组重排发生。非同源末端连接 (NHEJ) 是一种已知可保护基因组完整性的 DSB 修复机制,也与基因组易位、倒位、缺失和插入的产生有关。我们最近研究了 DSB 携带基因座的预损伤空间接近程度对 NHEJ 转录修复频率的影响,令人惊讶的是,我们没有发现它们之间的相关性。在这篇综述中,我们考虑了可能解释这些意外结果的各种模型。虽然 DSB 的移动是解释我们发现的必要条件,但关于这种运动的性质和时间仍有许多问题。