Target intelligence / Profile preview

DNA repair protein Rev1 (REV1)

Target
REV1
Molecular classification
Enzyme (DNA-directed polymerase), Y-family DNA polymerase, Translesion synthesis (TLS) polymerase
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Overview

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].

Other names
REV1REV1LAIBP80Alpha integrin-binding protein 80Rev1-like terminal deoxycytidyl transferaseDNA repair protein REV1 homologDNA polymerase REV1Rev1-like
02

Mechanism of action

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.

03

Biological functions

DNA damage tolerance via translesion synthesis (TLS)Bypass of DNA lesions (e.g., abasic sites, adducted guanine)Replication stress responseScaffolding for assembly of TLS machinery; polymerase switchingMaintenance of genome stabilitySomatic hypermutation
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Disease associations

Cancer (mutation accumulation through error-prone DNA synthesis)Genome instability disordersPossibly others related to defective DNA repair (e.g., sensitivity to replication stress, carcinogenesis)
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Safety considerations

Inhibition may sensitize normal cells to DNA-damaging agents, causing off-target genotoxicity or reduced genome stability[2].Mutagenic potential when active, leading to increased risk of secondary malignancies due to error-prone bypass and mutation accumulation[2][4].Therapeutic targeting needs to balance cancer kill versus preservation of normal tissue genome integrity[2].
06

Interacting drugs

No currently approved drugs directly targeting Rev1.

1 more in the full profile.

07

Biomarkers

REV1 protein expression and activity have been proposed as potential biomarkers in cancer for patient selection and monitoring therapy that targets TLS, but no validated biomarkers are established in clinical practice[2].

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