REV1

What is REV1 protein?

REV1 gene (REV1 DNA directed polymerase) is a protein coding gene which situated on the long arm of chromosome 2 at locus 2q11. REV1 protein, a member of the translesion synthesis DNA polymerase Y family, plays a critical role in DNA replication activities and is involved in the maintenance of genome integrit. This process is crucial for the cell's ability to replicate DNA past these lesions without causing mutations, thus preventing genomic instability. REV1 is also implicated in the production of both spontaneous and DNA damage-induced mutations, suggesting its importance in DNA repair mechanisms. The REV1 protein is consisted of 1251 amino acids and REV1 molecular weight is approximately 138.2 kDa.

What is the function of REV1 protein?

REV1 protein is a special DNA polymerase belonging to the DNA polymerase Y family in eukaryotes. It plays an important role in DNA replication, especially in transdamage DNA synthesis (TLS). The REV1 protein helps cells bypass damaged DNA bases, such as adjoint guanine bases and base-free sites, during DNA replication. The REV1 protein is involved in homologous recombination repair (HR) of DNA double strand breaks, acting synergically with FANCD2 in the presence of replication pressure to protect the newly replicated DNA strand from nuclease degradation. The REV1 protein contains the BRCT domain, which is very important in protein-protein interactions, and the REV1 protein may act as a scaffold protein to recruit DNA polymerase involved in TLS.

Fig1. Model of REV1 targeting to DNA breaks to prevent chromosome instability. (Yeran Yang, 2015)

REV1 Related Signaling Pathway

REV1 is a key protein in the TLS process, interacting with other Y family DNA polymerases such as Polη to help cells replicate at the site of DNA damage and maintain genome stability. In the immune response of B cells, REV1 participates in the hypermutation process of Ig gene through its catalytic activity, which affects the production of antibody diversity. REV1 may be involved in cell cycle regulation by affecting the function of cell cycle-related proteins, especially when DNA damage occurs. REV1 plays a role in DNA damage detection and response, interacts with a variety of DDR proteins, and participates in damage signal transmission and repair decision making.

REV1 Related Diseases

REV1 protein is associated with a variety of diseases, especially the occurrence, development and treatment responsiveness of cancer. Studies have shown that the level of REV1 expression varies significantly across different tumor types and is associated with patient prognosis. For example, in colorectal, ovarian, lung, breast, and gastric cancers, REV1 expression was significantly associated with prognostic measures such as disease-specific survival, disease-free survival, overall survival, and survival after progression. Low expression of REV1 was associated with a better prognosis for colorectal, gastric, and ovarian cancers, while high expression of REV1 was associated with a better prognosis for lung and breast cancer. In addition, genetic mutations in REV1 are associated with a patient's sensitivity to chemotherapy drugs and may affect tumor cells' responsiveness to chemotherapy.

Bioapplications of REV1

REV1 protein has a variety of potential applications in medical research and clinical therapy, especially in the field of tumor therapy. Since REV1 plays an important role in the protection of replication chains under DNA damage response and replication pressure, reducing REV1 levels can enhance the sensitivity of tumor cells to chemotherapy and effectively reduce the development of drug resistance in tumor cells. In addition, REV1 expression levels are associated with the prognosis of multiple cancers, including colorectal, ovarian, lung, breast, and stomach cancers, making it a potential biomarker and therapeutic target for these cancers. In terms of drug development, inhibitors of REV1 may improve therapeutic efficacy by enhancing the sensitivity of tumor cells to radiotherapy and certain chemotherapy drugs. At the same time, single nucleotide polymorphisms (SNPS) of REV1 are associated with drug sensitivity and contribute to the development of personalized medicine and precision therapy strategies.

Case Study 1: Anastasia D Stolyarenko, 2024

Eukaryotic REV1 serves as a scaffold protein for the coordination of DNA polymerases during DNA translesion synthesis. Besides this structural role, REV1 is a Y-family DNA polymerase with its own distributive deoxycytidyl transferase activity. However, data about the accuracy and efficiency of DNA synthesis by REV1 in the literature are contrasting. Here, researchers expressed and purified the full-length human REV1 from Saccharomyces cerevisiae and characterized its activity on undamaged DNA and a wide range of damaged DNA templates. They demonstrated that REV1 carried out accurate synthesis opposite 8-oxoG and O6-meG with moderate efficiency. It also replicated thymine glycol surprisingly well in an error-prone manner, but was blocked by the intrastrand 1,2-GG cisplatin crosslink.

Fig1. REV1 activity on DNA containing undamaged A, G, T or C.

Fig2. REV1 activity on DNA containing the AP site.

Case Study 2: Yunshang Chen, 2022

REV1 is the central member of the family of TLS polymerases, which participate in various DNA damage repair and tolerance pathways and play a significant role in maintaining genomic stability. However, the role of REV1 in tumors is rarely reported. In this study, researchers found that the expression of REV1 was significantly upregulated in lung cancer tissues compared with matched adjacent tissues and was associated with poor prognosis. Functional experiments demonstrated that REV1 silencing decreased the growth and proliferation capacity of lung cancer cells. Mechanistically, REV1 upregulated the expression of SERTAD2 in a Rad18-dependent manner, thereby promoting lung carcinogenesis. A novel REV1 inhibitor, JH-RE-06, suppressed lung tumorigenesis in vivo and in vitro and was shown to be safe and well tolerated.

Fig3. Protein levels of REV1, Rad18 and RPA32 in different cell lines.

Fig4. A549 and H1299 cells transfected with Flag-REV1 were harvested and examined by Western blot.

REV1 has several biochemical functions, for example, damaged DNA binding,deoxycytidyl transferase activity,metal ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by REV1 itself. We selected most functions REV1 had, and list some proteins which have the same functions with REV1. You can find most of the proteins on our site.

REV1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with REV1 here. Most of them are supplied by our site. Hope this information will be useful for your research of REV1.

REV3L;FHL2;POLH