DNA polymerase zeta catalytic subunit (REV3L)

DNA polymerase zeta catalytic subunit, encoded by the REV3L gene, is a specialized B-family DNA polymerase that plays a pivotal role in translesion synthesis (TLS) [1, 2]. TLS is a DNA damage tolerance mechanism that allows the replication machinery to bypass bulky lesions, such as those induced by UV radiation or cross-linking agents, which would otherwise stall replicative polymerases [2, 3]. While REV3L is essential for maintaining genome stability by preventing replication fork collapse, its activity is inherently error-prone and is a major source of DNA damage-induced mutagenesis [1, 4]. In clinical oncology, REV3L is a significant factor in chemoresistance, as it enables cancer cells to survive the DNA-damaging effects of platinum-based drugs and ionizing radiation [4, 5]. Research is currently focused on developing small-molecule inhibitors of the Pol zeta complex, such as those targeting the REV1-REV7-REV3L interface, to sensitize resistant tumors to standard-of-care treatments [3, 6]. By inhibiting this subunit, clinicians hope to overcome the adaptive resistance mechanisms that allow tumors to persist after DNA-damaging therapy [5, 6]. Citations: [1] UniProt Consortium (2023) P38601; [2] Gan et al. (2008) Cell Research; [3] Wojtaszek et al. (2019) Nature; [4] Sharma & Canman (2012) Cancer Biology & Therapy; [5] Wang et al. (2015) Cancer Letters; [6] Rizzo et al. (2018) DNA Repair.

Other names

REV3POLZREV3LDNA polymerase zeta catalytic subunitREV3-like DNA polymeraseZeta DNA polymerase catalytic subunit

Inhibition of translesion synthesis (TLS) to prevent the bypass of DNA lesions, thereby increasing the efficacy of DNA-damaging chemotherapeutic agents and inducing apoptosis in cancer cells.