Rev3l, also known as Protein reversion less 3-like, encodes the catalytic subunit of error-prone translesion synthesis polymerase ζ. It is crucial for the tolerance of DNA damage by inducing translesion synthesis (TLS), a DNA damage repair mechanism involved in bypassing DNA lesions during replication [4]. TLS is important for maintaining genome stability in the face of various DNA-damaging agents.

In multiple cancer types, Rev3l has been implicated. In non-small cell lung cancer (NSCLC) in the Jammu and Kashmir population, specific single nucleotide variants of Rev3l (rs1002481, rs462779, rs465646) were associated with an increased risk of NSCLC under the recessive model [1]. In NSCLC cell lines, cisplatin induced Rev3l expression, and overexpression of Rev3l conferred cisplatin resistance, while knockdown sensitized cells to cisplatin treatment [2]. In esophageal squamous cell carcinoma (ESCC), Rev3l was upregulated and correlated with lymph node metastasis and clinical stage. Downregulation of Rev3l decreased cell proliferation and invasive capacity and increased sensitivity to 5-fluorouracil [3]. Similar roles in conferring chemoresistance were seen in gliomas and cervical cancer, where Rev3l overexpression attenuated cisplatin-induced apoptosis, and knockdown enhanced sensitivity [5,6]. In a myelodysplastic syndrome patient, a Rev3l mutation (c.9253-6T>C) was associated with poor prognosis [7]. Also, in a Chinese population, the rs465646 polymorphism in the 3'UTR of Rev3l was associated with lung cancer susceptibility [8].

In conclusion, Rev3l is essential for translesion DNA synthesis and maintaining genome stability. Its role in conferring chemoresistance and its association with cancer susceptibility and progression in various cancer types highlight its importance in cancer research. Understanding Rev3l function through such studies may offer new therapeutic strategies for cancer treatment.