REV1 gene

The REV1 gene (REV1 stands for REV1 DNA-directed polymerase) is a protein-coding gene located on chromosome 2q11.2. An important paralog of this gene is POLI.

The REV1 gene encodes a protein with similarity to the S. cerevisiae mutagenesis protein Rev1. The Rev1 proteins contain a BRCT domain that is important for protein-protein interactions. The role of the human Rev1-like protein is thought to be that of a scaffold that recruits DNA polymerases involved in the translesion synthesis (TLS) of damaged DNA.

Diseases associated with REV1 include:

• xeroderma pigmentosum, variant type (X-PV)
• and
• Fanconi anemia, complementation group F.

Associated signaling pathways include translesion synthesis by Y-family DNA polymerases bypassing lesions on the DNA template and homology-directed repair.

The REV1 DNA-directed polymerase is a deoxycytidyltransferase that is involved in DNA repair. It transfers a dCMP residue (=2'deoxycytidine-5`monophosphate) from dCTP (=2'deoxycytidine-5`triphosphate) to the 3'-end of a DNA primer in a template-dependent reaction. The REV1-like polymerase can assist in the first step of bypassing abasic lesions by inserting a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents (Ikeh KE et al. 2021).

The function of REV1, which was previously known to facilitate the formation of new mutations through its function as a deoxycitidyltransferase, is now also known to facilitate protein-protein interactions with other TLS polymerases by folding into a scaffold molecule (Yamanaka K.et al. 2017). REV1 inhibitors that target specific interfaces of this CTD sensitize cancer cells to chemotherapy (Chatterjee N et al. 2020). REV1 also plays a role in the DSBR signaling pathway and suppresses apoptosis - processes known to be involved in radioresistance (Sui X et al. 2013).

1. Chatterjee N et al. (2020) A stapled POL kappa peptide targets REV1 to inhibit mutagenic translesion synthesis. Environ Mol Mutagen 61:830-836
2. Ikeh KE et al. (2021) REV1 Inhibition Enhances Radioresistance and Autophagy. Cancers (Basel) 13:5290.
3. Sui X et al. (2013) Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis 4:e838.
4. Yamanaka K et al. (2017) Inhibition of mutagenic translesion synthesis: A possible strategy for improving chemotherapy? PLoS Genet 13:e1006842.