Bohm Kaitlynne A, Wyrick John J
School of Molecular Biosciences, Washington State University, Pullman, WA, United States.
Front Genet. 2023 Jan 10;13:1102593. doi: 10.3389/fgene.2022.1102593. eCollection 2022.
Ultraviolet (UV) light is a pervasive threat to the DNA of terrestrial organisms. UV light induces helix-distorting DNA lesions, primarily cyclobutane pyrimidine dimers (CPDs) that form between neighboring pyrimidine bases. Unrepaired CPD lesions cause cytosine-to-thymine (C>T) substitutions in dipyrimidine sequences, which is the predominant mutation class in skin cancer genomes. However, many driver mutations in melanoma ( in the and oncogenes) do not fit this UV mutation signature. Recent studies have brought to light the intriguing hypothesis that these driver mutations may be induced by infrequent or atypical UV photoproducts, including pyrimidine 6-4 pyrimidone photoproducts (6-4PP) and thymine-adenine (TA) photoproducts. Here, we review innovative methods for mapping both canonical and atypical UV-induced photoproducts across the genome.
紫外线（UV）对陆地生物的DNA构成普遍威胁。紫外线会诱导使螺旋结构扭曲的DNA损伤，主要是相邻嘧啶碱基之间形成的环丁烷嘧啶二聚体（CPD）。未修复的CPD损伤会导致二嘧啶序列中的胞嘧啶到胸腺嘧啶（C>T）替换，这是皮肤癌基因组中主要的突变类型。然而，黑色素瘤中的许多驱动突变（如BRAF和NRAS癌基因中的突变）并不符合这种紫外线突变特征。最近的研究揭示了一个有趣的假说，即这些驱动突变可能是由罕见或非典型的紫外线光产物诱导的，包括嘧啶6-4嘧啶酮光产物（6-4PP）和胸腺嘧啶-腺嘌呤（TA）光产物。在这里，我们综述了用于绘制全基因组中典型和非典型紫外线诱导光产物图谱的创新方法。
