DNA polymerase zeta catalytic subunit (REV3L) mRNA (REV3L mRNA)

REV3L encodes the catalytic subunit of DNA polymerase zeta (Pol ζ), a specialized B-family DNA polymerase essential for translesion synthesis (TLS) (UniProt: P38601). TLS allows the replication machinery to bypass DNA lesions that would otherwise stall replication forks, thereby maintaining genome integrity but often at the cost of increased mutagenesis (PubMed: 25670504). In the context of oncology, REV3L is frequently upregulated in various cancers and contributes to resistance against DNA-damaging chemotherapeutics, such as cisplatin and ionizing radiation (PubMed: 22344312). By bypassing the DNA crosslinks or adducts formed by these treatments, REV3L enables cancer cell survival and promotes the acquisition of further mutations. Targeting REV3L mRNA using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) aims to deplete Pol ζ levels, effectively blocking TLS and sensitizing tumor cells to standard-of-care DNA-damaging agents (PubMed: 18413743). While promising as a combination therapy, challenges include the essential role of REV3L in normal development—as evidenced by embryonic lethality in mouse models—and the potential for systemic toxicity if TLS is inhibited in healthy tissues (PubMed: 10541554).

Other names

REV3POLZDNA polymerase zeta catalytic subunit mRNAREV3-like DNA directed polymerase mRNA

Antisense-mediated mRNA degradation or RNA interference leading to the depletion of DNA polymerase zeta catalytic subunit, which inhibits translesion synthesis and increases the sensitivity of cancer cells to DNA-damaging agents (PubMed: 18413743).