Eukaryotic DNA is organized in nucleosomes, which package DNA and regulate its accessibility to transcription, replication, recombination and repair. Here, we show that in living cells nucleosomes protect DNA from high-energy radiation and reactive oxygen species. We combined sequence-based methods (ATAC-seq and BLISS) to determine the position of both nucleosomes and double strand breaks (DSBs) in the genome of nucleosome-rich malignant mesothelioma cells, and of the same cells partially depleted of nucleosomes. The results were replicated in the human MCF-7 breast carcinoma cell line. We found that, for each genomic sequence, the probability of DSB formation is directly proportional to the fraction of time it is nucleosome-free; DSBs accumulate distal from the nucleosome dyad axis. Nucleosome free regions and promoters of actively transcribed genes are more sensitive to DSB formation, and consequently to mutation. We argue that this may be true for a variety of chemical and physical DNA damaging agents.

中文翻译：

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核小体有效地保护 DNA 免受活细胞中的辐射损伤。

真核 DNA 在核小体中组织，核小体包装 DNA 并调节其转录、复制、重组和修复的可及性。在这里，我们证明在活细胞中核小体可以保护 DNA 免受高能辐射和活性氧的影响。我们结合基于序列的方法（ATAC-seq 和 BLISS）来确定富含核小体的恶性间皮瘤细胞以及部分耗尽核小体的相同细胞的基因组中核小体和双链断裂（DSB）的位置。结果在人 MCF-7 乳腺癌细胞系中得到复制。我们发现，对于每个基因组序列，DSB 形成的概率与其无核小体的时间比例成正比；DSB 在远离核小体二轴的地方聚集。活跃转录基因的无核小体区域和启动子对 DSB 形成更敏感，从而对突变更敏感。我们认为这对于多种化学和物理 DNA 损伤剂来说可能都是正确的。