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DNA repair protein Rev1 (REV1) is a specialized, eukaryotic Y-family DNA-directed polymerase central to the translesion synthesis (TLS) pathway, a critical DNA damage tolerance mechanism. Rev1 facilitates bypass of replication-blocking DNA lesions such as abasic sites and exocyclic guanine adducts by using a unique protein-template mechanism: it evicts the template base from the DNA helix and instead, its arginine side chain guides the insertion of cytosine, regardless of the template nucleotide identity[1][3][4]. In addition to its direct enzymatic activity as a deoxycytidyl transferase, Rev1 plays a scaffolding role, organizing and recruiting other TLS DNA polymerases (such as Pol κ, Pol ι, Pol η, and Pol ζ)[2][4]. This function is essential for polymerase switching during lesion bypass. While Rev1 contributes to cell survival under conditions of DNA damage and replication stress, its error-prone mechanism can introduce mutations, serving as a double-edged sword in cancer development and therapy response[2][4]. Emerging research highlights REV1 as a biomarker and potential therapeutic target, especially for strategies that exploit its role to enhance chemotherapeutic efficacy or limit mutagenesis[2].
For inhibitors: Block translesion synthesis and error-prone DNA damage bypass. For direct enzymatic function: Incorporates cytosine across various DNA lesions using protein-template mechanism.
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