Morledge-Hampton Benjamin, Selvam Kathiresan, Chauhan Manish, Goodman Alan G, Wyrick John J
School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USA.
Paul G. Allen School for Global Health, Washington State University, Pullman, Washington 99164, USA.
Genome Res. 2025 Feb 14;35(2):257-267. doi: 10.1101/gr.279605.124.
Cyclobutane pyrimidine dimers (CPDs) are formed in DNA following exposure to ultraviolet (UV) light and are mutagenic unless repaired by nucleotide excision repair (NER). It is known that CPD repair rates vary in different genome regions owing to transcription-coupled NER and differences in chromatin accessibility; however, the impact of regional chromatin organization on CPD formation remains unclear. Furthermore, nucleosomes are known to modulate UV damage and repair activity, but how these damage and repair patterns are affected by the overarching chromatin domains in which these nucleosomes are located is not understood. Here, we generated a new CPD damage map in S2 cells using CPD-seq and analyzed it alongside existing excision repair-sequencing (XR-seq) data to compare CPD damage formation and repair rates across five previously established chromatin types in This analysis revealed that repair activity varies substantially across different chromatin types, whereas CPD formation is relatively unaffected. Moreover, we observe distinct patterns of repair activity in nucleosomes located in different chromatin types, which we show is owing to domain-specific differences in nucleosome repeat length (NRL). These findings indicate that NRL is altered in different chromatin types in and that changes in NRL modulate the repair of UV lesions.
环丁烷嘧啶二聚体（CPDs）在DNA暴露于紫外线（UV）后形成，并且具有致突变性，除非通过核苷酸切除修复（NER）进行修复。已知由于转录偶联的NER以及染色质可及性的差异，CPD修复率在不同基因组区域有所不同；然而，区域染色质组织对CPD形成的影响仍不清楚。此外，已知核小体可调节紫外线损伤和修复活性，但这些损伤和修复模式如何受到这些核小体所在的总体染色质结构域的影响尚不清楚。在这里，我们使用CPD-seq在S2细胞中生成了一个新的CPD损伤图谱，并将其与现有的切除修复测序（XR-seq）数据一起进行分析，以比较在五种先前确定的染色质类型中CPD损伤的形成和修复率。该分析表明，修复活性在不同染色质类型之间有很大差异，而CPD的形成相对不受影响。此外，我们在位于不同染色质类型中的核小体中观察到不同的修复活性模式，我们发现这是由于核小体重复长度（NRL）的结构域特异性差异所致。这些发现表明，在[具体物种]中不同染色质类型的NRL发生了改变，并且NRL的变化调节了紫外线损伤的修复。
