Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, Washington, USA.
Genetics and Cell Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington, USA.
J Biol Chem. 2023 Sep;299(9):105118. doi: 10.1016/j.jbc.2023.105118. Epub 2023 Jul 30.
DNA in eukaryotic cells is packaged into the compact and dynamic structure of chromatin. This packaging is a double-edged sword for DNA repair and genomic stability. Chromatin restricts the access of repair proteins to DNA lesions embedded in nucleosomes and higher order chromatin structures. However, chromatin also serves as a signaling platform in which post-translational modifications of histones and other chromatin-bound proteins promote lesion recognition and repair. Similarly, chromatin modulates the formation of DNA damage, promoting or suppressing lesion formation depending on the chromatin context. Therefore, the modulation of DNA damage and its repair in chromatin is crucial to our understanding of the fate of potentially mutagenic and carcinogenic lesions in DNA. Here, we survey many of the landmark findings on DNA damage and repair in chromatin over the last 50 years (i.e., since the beginning of this field), focusing on excision repair, the first repair mechanism studied in the chromatin landscape. For example, we highlight how the impact of chromatin on these processes explains the distinct patterns of somatic mutations observed in cancer genomes.
真核细胞中的 DNA 被包装成紧凑和动态的染色质结构。这种包装对 DNA 修复和基因组稳定性来说是一把双刃剑。染色质限制了修复蛋白对嵌入核小体和更高阶染色质结构中的 DNA 损伤的访问。然而，染色质也作为一个信号平台，其中组蛋白和其他染色质结合蛋白的翻译后修饰促进损伤识别和修复。同样，染色质调节 DNA 损伤的形成，根据染色质的上下文促进或抑制损伤的形成。因此，在染色质中调节 DNA 损伤及其修复对于我们理解 DNA 中潜在致突变和致癌损伤的命运至关重要。在这里，我们调查了过去 50 年来（即该领域开始以来）在染色质中 DNA 损伤和修复的许多里程碑式发现，重点关注切除修复，这是在染色质景观中研究的第一个修复机制。例如，我们强调了染色质对这些过程的影响如何解释在癌症基因组中观察到的不同体细胞突变模式。
