REV7 - a small but mighty regulator of genome maintenance and cancer development - comprehensive review

Sep 23, 2026

Uploaded by Finn

REV7, a HORMA-domain family protein also known as MAD2B, MAD2L2, and FANCV, is central to multiple genome stability pathways. It functions as a member of polymerase z that enables DNA damage tolerance via translesion synthesis, while also regulating accurate cell-cycle progression by preventing premature mitotic advance. REV7 further influences double-strand break repair pathway choice through the mammalian shieldin complex. Because genome instability drives cancer, REV7 is linked to ovarian, glioma, breast cancer, melanoma, and small-cell lung cancer, where high expression correlates with poor prognosis and treatment resistance. Early evidence suggests REV7 suppression increases cisplatin sensitivity.

LanguageEnglish

CategoryHealthcare

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Pages26

Reading Time1 h 6 min

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Introduction

REV7 in genome stability and cancer

Conformational changes of the REV7 HORMA domain protein drive its function in multiple cellular pathways

Discovery and naming of REV7

TYPE Review PUBLISHED 07 January 2025 DOI 10.3389/fonc.2024.1516165 OPEN ACCESS EDITED BY Nimrat Chatterjee, University of Vermont, United States REVIEWED BY Eswari Dodagatta-Marri, University of California, San Francisco, United States Kulbhushan Thakur, University of Delhi, India *CORRESPONDENCE Mitch McVey [mitch.mcvey@tufts.edu](mitch.mcvey@tufts.edu)[ ](mitch.mcvey@tufts.edu)Lara R. Maggs [lara.maggs@tufts.edu](lara.maggs@tufts.edu) RECEIVED 23 October 2024 ACCEPTED 12 December 2024 PUBLISHED 07 January 2025 CITATION Maggs LR and McVey M (2025) REV7: a small but mighty regulator of genome maintenance and cancer development. Front. Oncol. 14:1516165 . doi: 10.3389/fonc.2024.1516165 COPYRIGHT © 2025 Maggs and McVey. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. REV7: a small but mighty regulator of genome maintenance and cancer development Lara R. Maggs* and Mitch McVey* 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 asa member of polymerase z, 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. Additionally, REV7 supports genome integrity by directing double-strand break repair pathway choice as part of the recently characterized mammalian shieldin complex. Given that genome instability is a hallmark of cancer, it is unsurprising that REV7, with its numerous genome maintenance roles, is implicated in multiple malignancies, including ovarian cancer, glioma, breast cancer, malignant melanoma, and small-cell lung cancer. Moreover, high REV7 expression is associated with poor prognoses and treatment resistance in these and other cancers. Promisingly, early studies indicate that REV7 suppression enhances sensitivity to chemotherapeutics, including cisplatin. This review aims to provide a comprehensive overview of REV7’s myriad roles in genome maintenance and other functions as well as offer an updated summary of its connections to cancer and treatment resistance. KEYWORDS REV7, genome stability, DNA damage response, cancer, chemotherapeutic resistance, chromatin Introduction Despite its small size of just 211 amino acids, REV7 plays an outsized role in promoting genome stability and cell viability. It participates in several DNA damage response pathways, including translesion synthesis, interstrand crosslink repair, and double-strand break repair. As a component of the shieldin complex, REV7 regulates double-strand break repair pathway choice by protecting single-stranded DNA from nucleolytic processing, thereby promoting repair via non-homologous end joining. Additionally, REV7 functions in cell cycle regulation, antibody diversiﬁcation, B cell survival, and primordial germ cell Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) development. Given its involvement in myriad cellular processes, it is not surprising that REV7 has a substantial impact on cancer biology. Clinically, REV7 is implicated in various cancers, including lung, ovarian, and skin cancers (Table 1) . Furthermore, REV7 contributes to chemotherapeutic resistance, making it an appealing target for pharmacologic inhibition to enhance the sensitivity of cancer cells to chemotherapy. In this review, we present a thorough examination of the m

FAQs

What roles does REV7 play in maintaining genome stability?

REV7 supports genome integrity through DNA damage response functions including translesion synthesis, double-strand break repair, and regulation of repair pathway choice as part of the shieldin complex.

How is REV7 connected to cancer and clinical outcomes?

REV7 is implicated in multiple malignancies, and high REV7 expression is associated with poor prognoses and treatment resistance across these cancers.

How might inhibiting REV7 affect cancer treatment response?

Early studies indicate that suppressing REV7 can enhance sensitivity to chemotherapeutics such as cisplatin.

Sep 23, 2026

Uploaded by Finn