DNA repair and cell cycle regulation are potential biological fields to develop molecular targeting therapies for cancer. Human REV7 was originally discovered as a homologous molecule to yeast Rev7, which is involved in DNA damage response and mutagenesis, and as the second homolog of yeast Mad2, involved in the spindle assembly checkpoint. Although REV7 principally functions in the fields of DNA repair and cell cycle regulation, many binding partners of REV7 have been identified using comprehensive analyses in the past decade, and the significance of REV7 is expanding in various other biological fields, such as gene transcription, epigenetics, primordial germ cell survival, neurogenesis, intracellular signaling, and microbial infection. In addition, the clinical significance of REV7 has been demonstrated in studies using human cancer tissues, and investigations in cancer cell lines and animal models have revealed the greater impacts of REV7 in cancer biology, which makes it an attractive target molecule for cancer management. This review focuses on the functions of REV7 in human cancer and discusses the utility of REV7 for cancer management with a summary of the recent development of inhibitors targeting REV7.
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http://dx.doi.org/10.3390/cancers15061721 | DOI Listing |
Front Oncol
January 2025
Department of Biology, Tufts University, Medford, MA, United States.
REV7, also known as MAD2B, MAD2L2, and FANCV, is a HORMA-domain family protein crucial to multiple genome stability pathways. REV7's canonical role is as a member of polymerase ζ, a specialized translesion synthesis polymerase essential for DNA damage tolerance. REV7 also ensures accurate cell cycle progression and prevents premature mitotic progression by sequestering an anaphase-promoting complex/cyclosome activator.
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December 2024
Department of Biochemistry, Indian Institute of Science Bangalore, Bengaluru, India.
Head Neck
November 2024
Department of Otorhinolaryngology, Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Background: REV7 is a multifunctional protein involved in various biological processes, including DNA damage response. REV7 expression in human cancer cells influences sensitivity to DNA-damaging agents, and its high expression level is reportedly associated with a poor prognosis in many carcinomas. However, the significance of REV7 expression in human papillomavirus 16-negative oropharyngeal squamous cell carcinoma (OPSCC) remains unclear.
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November 2024
Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA. Electronic address:
REV7 is a HORMA (Hop1, Rev7, Mad2) family adaptor protein best known as an accessory subunit of the translesion synthesis (TLS) DNA polymerase ζ (Polζ). In this role, REV7 binds REV3, the catalytic subunit of Polζ, by locking REV7-binding motifs (RBMs) in REV3 underneath the REV7 safety-belt loop. The same mechanism is used by REV7 to interact with RBMs from other proteins in DNA damage response (DDR) and mitosis.
View Article and Find Full Text PDFAdv Sci (Weinh)
July 2024
Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
DNA damage plays a significant role in the tumorigenesis and progression of the disease. Abnormal DNA repair affects the therapy and prognosis of cancer. In this study, it is demonstrated that the deubiquitinase USP25 promotes non-homologous end joining (NHEJ), which in turn contributes to chemoresistance in cancer.
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