Rev3l-flox Mouse

REV3L, also known as Protein reversion less 3-like, encodes the catalytic subunit of error-prone translesion synthesis polymerase zeta. It is involved in DNA damage repair pathways, specifically translesion DNA synthesis (TLS), which allows DNA replication to proceed past damaged sites. This function is crucial for maintaining genome stability, but its error-prone nature can also lead to mutagenesis, making it relevant in cancer research [1,2,3,4,5,6,8].

In various cancers, REV3L has shown significant associations. In the Jammu and Kashmir population, certain REV3L single nucleotide variants (rs1002481, rs462779, rs465646) were strongly associated with an increased risk of non-small cell lung cancer (NSCLC) [1]. In NSCLC cell lines, cisplatin treatment induced REV3L expression, and overexpression of REV3L conferred cisplatin resistance, while knockdown sensitized the cells to cisplatin, suggesting it could be a novel target for NSCLC chemotherapy [2]. Similar findings were seen in esophageal squamous cell carcinoma, where REV3L was upregulated, and its downregulation decreased cell proliferation, invasive capacity, and increased chemosensitivity to 5-fluorouracil [3]. In gliomas, REV3L was overexpressed, and its downregulation using RNA interference enhanced cisplatin sensitivity [5]. In cervical cancer, the expression of REV3L was higher in cancer tissues, and its suppression or overexpression affected cell proliferation, colony formation, and cisplatin sensitivity [6]. Also, in a myelodysplastic syndrome patient, a REV3L mutation (c.9253-6T>C) was associated with poor prognosis [7]. In a Chinese population, the rs465646 polymorphism in REV3L was associated with lung cancer susceptibility [8]. In NSCLC, circular RNA PRMT5 promoted cisplatin resistance via the miR-4458/REV3L axis [9].

In conclusion, REV3L is essential for translesion DNA synthesis, playing a significant role in maintaining genome stability. Its dysregulation is associated with various cancers, including NSCLC, esophageal, glioma, cervical, and myelodysplastic syndromes. Understanding REV3L's function and its associated genetic variations can potentially lead to new diagnostic and therapeutic strategies for these diseases.