Major roles of cyclobutane pyrimidine dimers, nucleotide excision repair and ATR in the alternative splicing response to UV irradiation

Alternative splicing (AS) is the main process that amplifies DNA information and is a crucial target of signaling cascades resulting from UV irradiation of human cells. The specific impact of UV-induced cyclobutane pyrimidine dimers (CPDs) at the transcriptional and AS levels has not been addressed. By using a CPD photolyase, a flavoenzyme that directly reverts CPDs, we analyze the contribution of this lesion to the expression program in human keratinocytes.

可变剪接（Alternative splicing, AS）是扩增DNA遗传信息的核心过程，同时也是人类细胞经紫外线照射后所激活的信号级联反应的关键靶标。紫外线诱导产生的环丁烷嘧啶二聚体（cyclobutane pyrimidine dimers, CPDs）在转录水平与可变剪接层面的具体影响尚未得到阐明。本研究通过使用可直接修复CPDs的黄素酶——CPD光解酶，分析了该DNA损伤在人类角质形成细胞的基因表达程序中所发挥的作用。