DNA polymerase zeta catalytic subunit (REV3-like) (REV3L or Rev3)

DNA polymerase zeta catalytic subunit (REV3-like) is the largest and catalytically active component of Pol ζ, a B-family DNA polymerase that is crucial for translesion DNA synthesis—a pathway allowing DNA replication past lesions or damage that would otherwise stall replication forks. REV3L forms a multi-subunit enzyme complex with REV7 (also MAD2L2), POLD2, and POLD3, enabling tolerance to diverse DNA lesions and promoting genome stability in eukaryotic cells. The holoenzyme has a pentameric ring-like structure, and unlike other B-family DNA polymerases, the exonuclease domain of REV3L is inactive (lacks proofreading). Loss of REV3L function leads to genomic instability and cell death, while its activity is leveraged by cancer cells to survive genotoxic stress, making it a promising—but therapeutically challenging—target.

Other names

REV3L (human gene symbol commonly used)Rev3p (yeast ortholog)DNA polymerase zeta catalytic subunitREV3-like

Extension step of translesion synthesis—REV3L (Pol ζ) extends primers across beyond replication-blocking DNA lesions, often working with other TLS polymerases (e.g., REV1, Pol η)