The values used to build graphs in Fig 4.

Genome instability is a major force driving tumorigenesis. The ssDNA-binding protein complex CTC1-STN1-TEN1 (CST) plays a pivotal role in maintaining genome stability by countering replication stress, modulating DNA damage repair, and maintaining telomere integrity. Despite its well-documented role in genome maintenance, the involvement of CST in skin cancer development has yet to be investigated. We recently found that CST localizes at stalled DNA replication sites after UV exposure and may suppress the unwanted repriming activity, suggesting a potential role of CST in suppressing genome instability caused by UV damage. In this study, we first analyzed CST expression and alterations in cutaneous melanoma database and found that the CST genes are frequently altered in cutaneous melanoma and their expression is significantly downregulated in melanoma samples compared to normal tissues. We then generated a conditional knockout (cKO) mouse model with STN1 deficiency specifically in melanocytes to investigate its role in skin cancer formation. Upon chronic exposure to UV irradiation, STN1-deficient mice exhibit no obvious difference in melanoma incidence compared to control littermates, suggesting that STN1 downregulation in mature melanocytes has no significant effect on UV-induced skin cancer development in lab mice.基因组不稳定性是驱动肿瘤发生的核心驱动力。CTC1-STN1-TEN1（CST）单链DNA（single-stranded DNA, ssDNA）结合蛋白复合物通过拮抗复制应激、调控DNA损伤修复以及维持端粒完整性，在基因组稳定性维持中发挥关键作用。尽管CST在基因组维持中的功能已有充分文献支撑，但目前尚无研究探讨其在皮肤癌发生发展中的参与作用。我们近期发现，CST在紫外线（ultraviolet, UV）照射后会靶向定位至停滞的DNA复制位点，并可抑制异常的DNA重新引发活性，这提示CST在抑制紫外线损伤诱导的基因组不稳定性方面存在潜在功能。本研究首先对皮肤黑色素瘤数据库中的CST表达与变异特征进行分析，结果显示CST基因在皮肤黑色素瘤中频繁发生变异，且相较于正常组织，黑色素瘤样本中CST基因的表达水平显著下调。随后，我们构建了黑素细胞特异性STN1缺陷的条件性敲除（conditional knockout, cKO）小鼠模型，以探究其在皮肤癌发生中的作用。在长期紫外线辐照处理后，STN1缺陷型小鼠与同窝对照小鼠的黑色素瘤发生率无显著差异，这表明在实验小鼠体内，成熟黑素细胞中STN1的表达下调对紫外线诱导的皮肤癌发生无显著影响。