REV1基因属于Y家族DNA聚合酶（Y-family DNA polymerases）基因家族，该家族以跨损伤合成（translesion synthesis, TLS）能力著称，即在DNA损伤位点绕过损伤进行复制，帮助细胞应对复制压力。REV1的核心功能是作为跨损伤合成途径的关键调控因子，其表达产物REV1蛋白兼具DNA聚合酶活性和支架蛋白作用。它通过锌指结构域（zinc finger domain）与其他TLS聚合酶（如Polζ、Polη等）相互作用，协调它们在损伤位点的招募和替换，确保DNA复制的延续。REV1的生物学特点包括：偏好与脱氧胞苷（dC）结合，在复制叉停滞时优先插入dC对抗损伤；其N端BRCA1 C端（BRCT）结构域参与蛋白相互作用，C端区域则负责聚合酶活性调控。主要作用位点为DNA损伤区域，尤其在紫外线诱导的嘧啶二聚体或化学加合物位点发挥作用。突变会导致跨损伤合成功能缺陷，引发基因组不稳定、突变累积，与癌症（如黑色素瘤、肺癌）易感性增加相关。研究发现REV1缺失的小鼠会出现胚胎致死或自发肿瘤率升高。该基因过表达时可能通过错误跨越损伤增加突变负荷，促进肿瘤进展；而表达降低则导致复制叉崩溃和染色体断裂，加剧细胞凋亡。REV1与化疗耐药性密切相关，某些癌细胞通过上调REV1逃避铂类药物（如顺铂）的DNA损伤效应。Y家族共性包括：低复制忠实性（易出错）、松散催化口袋结构（允许损伤DNA模板进入）以及 ubiquitin-binding domain（泛素结合域）介导的翻译后调控。目前"REV1"中文译名存在争议，部分文献保留英文原名以避免与酵母REV7等混淆。

这个基因编码的蛋白质与相似性的酿酒酵母突变蛋白修订版1。的修订版1蛋白含有一个BRCT域，这是在蛋白质 - 蛋白质相互作用重要。为人类修订版1样蛋白A建议的作用是作为新兵参与受损DNA的合成跨损伤（TLS）DNA聚合酶的支架。两个编码不同蛋白质可变剪接转录物变体已被发现。 [由RefSeq的，2008年7月提供]

The REV1 gene encodes a critical regulatory subunit of the Y-family DNA polymerases, a specialized class of enzymes characterized by their ability to perform translesion synthesis (TLS), a mechanism that allows DNA replication to proceed past obstructive lesions on the template strand. Unlike high-fidelity replicative polymerases, REV1 does not primarily act as a standalone replicative enzyme but functions as a versatile scaffold and regulator that coordinates the assembly of the TLS polymerase complex, particularly by recruiting and stabilizing the catalytic subunit Pol ζ (REV3) at sites of DNA damage. This coordination is mediated by specific protein-protein interactions, including the N-terminal BRCA1 C-terminal (BRCT) domain and zinc finger motifs, which facilitate the dynamic exchange of polymerases at stalled replication forks. REV1 exhibits a strong nucleotide preference for inserting deoxycytidine (dC) opposite damaged bases, a feature that is particularly relevant during the repair of UV-induced pyrimidine dimers and chemical adducts, thereby helping to maintain replication continuity in the face of genotoxic stress. The structural flexibility of the Y-family catalytic pockets, which permits the accommodation of distorted DNA templates, comes at the cost of reduced fidelity, meaning that REV1-mediated TLS is inherently error-prone and can contribute to mutagenesis if not tightly controlled. Consequently, dysregulation of REV1 has significant implications for genomic stability and disease; while its absence in mouse models leads to embryonic lethality or increased spontaneous tumorigenesis due to replication fork collapse and chromosomal breakage, aberrant overexpression in human cells can drive tumor progression by increasing the mutational load and promoting genetic instability. This dual role is clinically relevant in cancer biology, where elevated REV1 expression has been linked to increased resistance to platinum-based chemotherapeutics such as cisplatin, as cancer cells exploit enhanced TLS capacity to survive DNA-damaging treatments, while simultaneously contributing to the accumulation of mutations that fuel the evolution of aggressive phenotypes in malignancies such as melanoma and lung cancer.

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