DNA double-strand breaks (DSBs) are highly deleterious lesions, responsible for mutagenesis, chromosomal translocation or cell death. DSB repair (DSBR) is therefore a critical part of the DNA damage response (DDR) to restore molecular and genomic integrity. In humans, this process is achieved through different pathways with various outcomes. The balance between DSB repair activities varies depending on cell types, tissues or individuals. Over the years, several methods have been developed to study variations in DSBR capacity. Here, we mainly focus on functional techniques, which provide dynamic information regarding global DSB repair proficiency or the activity of specific pathways. These methods rely on two kinds of approaches. Indirect techniques, such as pulse field gel electrophoresis (PFGE), the comet assay and immunofluorescence (IF), measure DSB repair capacity by quantifying the time-dependent decrease in DSB levels after exposure to a DNA-damaging agent. On the other hand, cell-free assays and reporter-based methods directly track the repair of an artificial DNA substrate. Each approach has intrinsic advantages and limitations and despite considerable efforts, there is currently no ideal method to quantify DSBR capacity. All techniques provide different information and can be regarded as complementary, but some studies report conflicting results. Parameters such as the type of biological material, the required equipment or the cost of analysis may also limit available options. Improving currently available methods measuring DSBR capacity would be a major step forward and we present direct applications in mechanistic studies, drug development, human biomonitoring and personalized medicine, where DSBR analysis may improve the identification of patients eligible for chemo- and radiotherapy.

中文翻译：

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人类细胞中 DNA 双链断裂修复能力的评估：当前功能方法的重要概述。

DNA 双链断裂 (DSB) 是高度有害的病变，负责诱变、染色体易位或细胞死亡。因此，DSB 修复 (DSBR) 是 DNA 损伤反应 (DDR) 恢复分子和基因组完整性的关键部分。在人类中，这个过程是通过不同的途径实现的，结果也各不相同。DSB 修复活动之间的平衡因细胞类型、组织或个体而异。多年来，已经开发了多种方法来研究 DSBR 容量的变化。在这里，我们主要关注功能技术，它提供有关全球 DSB 修复能力或特定途径活动的动态信息。这些方法依赖于两种方法。间接技术，例如脉冲场凝胶电泳 (PFGE)、彗星分析和免疫荧光 (IF)，通过量化暴露于 DNA 损伤剂后 DSB 水平的时间依赖性降低来测量 DSB 修复能力。另一方面，无细胞分析和基于报告基因的方法直接跟踪人工 DNA 底物的修复。每种方法都有其固有的优点和局限性，尽管付出了相当大的努力，但目前还没有理想的方法来量化 DSBR 容量。所有技术都提供不同的信息，可以被视为互补，但一些研究报告了相互矛盾的结果。生物材料类型、所需设备或分析成本等参数也可能限制可用的选择。改进目前可用的测量 DSBR 能力的方法将是向前迈出的重要一步，我们将直接应用于机理研究、药物开发、