UV-Induced DNA Damage and Mutagenesis in Chromatin.
UV-Induced DNA Damage and Mutagenesis in Chromatin.
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DOI：
10.1111/php.12646
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发表时间：
2017-01
影响因子：
3.3
通讯作者：
Smerdon MJ
中科院分区：
文献类型：
--
作者：
Mao P;Wyrick JJ;Roberts SA;Smerdon MJ
紫外线辐射引起DNA双螺旋扭曲的光损伤，如果不修复，可能导致严重的生物后果，包括诱变或细胞死亡。在真核生物中，紫外线损伤的形成和修复都发生在染色质的背景下，其中基因组DNA与组蛋白一起包装成核小体和高级染色质结构。在这里，我们回顾了染色质如何影响真核细胞中紫外光产物的形成。我们描述了最初的发现，核小体和其他DNA结合蛋白诱导特征的“光足迹”在紫外光产物的形成。我们还描述了最近的进展，在全基因组的方法映射紫外线损伤，这呼应了早期的生化研究，并强调了核小体和转录因子在紫外线损伤的形成和修复在前所未有的分辨率的作用。最后，我们讨论了我们目前对紫外线诱导的DNA损伤的分布和修复如何影响人类皮肤癌中的诱变的理解。紫外线诱导的CPD二聚体的形成更频繁地发生在'出'旋转设置（由明亮的蓝色闪电）比在'在'旋转设置（微弱的蓝色闪电）在核小体DNA。局部DNA迁移率的相对水平由基于来自1id3核小体结构的B因子的色标表示，其中具有高B因子的DNA区域（即，高迁移率）被染成红色，而具有相对低B因子的DNA区域（即，低迁移率）是蓝色的。
UV radiation induces photolesions that distort the DNA double helix and, if not repaired, can cause severe biological consequences, including mutagenesis or cell death. In eukaryotes, both the formation and repair of UV damage occur in the context of chromatin, in which genomic DNA is packaged with histones into nucleosomes and higher-order chromatin structures. Here, we review how chromatin impacts the formation of UV photoproducts in eukaryotic cells. We describe the initial discovery that nucleosomes and other DNA-binding proteins induce characteristic ‘photofootprints’ during the formation of UV photoproducts. We also describe recent progress in genome-wide methods for mapping UV damage, which echoes early biochemical studies, and highlights the role of nucleosomes and transcription factors in UV damage formation and repair at unprecedented resolution. Finally, we discuss our current understanding of how the distribution and repair of UV-induced DNA damage influence mutagenesis in human skin cancers. Formation of UV-induced CPD dimers occurs more frequently at ‘out’ rotational settings (indicated by bright blue lightning bolts) than at ‘in’ rotational settings (faint blue lightning bolts) in nucleosomal DNA. The relative level of local DNA mobility is represented by a color scale based on the B-factor from the 1id3 nucleosome structure, where DNA regions with a high B-factor (i.e., high mobility) are colored red, and DNA regions with a relatively low B-factor (i.e., low mobility) are colored blue.