REV1 (REV1 DNA directed polymerase)
- symbol:
- REV1
- locus group:
- protein-coding gene
- location:
- 2q11.2
- gene_family:
- Polymerases, DNA-directed
- alias symbol:
- None
- alias name:
- None
- entrez id:
- 51455
- ensembl gene id:
- ENSG00000135945
- ucsc gene id:
- uc002tad.4
- refseq accession:
- NM_016316
- hgnc_id:
- HGNC:14060
- approved reserved:
- 2001-01-10
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。
This gene encodes a protein with similarity to the S. cerevisiae mutagenesis protein Rev1. The Rev1 proteins contain a BRCT domain, which is important in protein-protein interactions. A suggested role for the human Rev1-like protein is as a scaffold that recruits DNA polymerases involved in translesion synthesis (TLS) of damaged DNA. Two alternatively spliced transcript variants that encode different proteins have been found. [provided by RefSeq, Jul 2008]
Gene Ontology
Subcellular localization of REV1 (and its protein):
- plasma membrane
- cytoplasm
- extracellular
- golgi
- vesicle
- cytoskeleton
- endoplasmic reticulum
- nucleus
- endosome
- lysosome
- mitochondrion
Gene Ontology (GO) terms for REV1:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| 3460 Fanconi anemia pathway [PATH:hsa03460] |
| Name |
|---|
| DNA Damage Bypass |
| DNA Repair |
| Termination of translesion DNA synthesis |
| Translesion synthesis by POLI |
| Translesion synthesis by POLK |
| Translesion synthesis by REV1 |
| Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template |
| Disease | Score | NofPmids | NofSnps | Source |
| Malignant neoplasm of lung | 0.00764398 | 4 | 1 | BeFree_GAD |
| Meningioma | 0.002367032 | 1 | 0 | GAD |
| Cervical Intraepithelial Neoplasia | 0.002367032 | 1 | 0 | GAD |
| Squamous cell carcinoma | 0.002367032 | 1 | 0 | GAD |
| Meningeal Neoplasms | 0.002367032 | 1 | 0 | GAD |
| Uterine Cervical Neoplasm | 0.002367032 | 1 | 0 | GAD |
| Chronic Lymphocytic Leukemia | 0.002367032 | 1 | 0 | GAD |
| Malignant neoplasm of breast | 0.002367032 | 1 | 0 | GAD |
| Brucella melitensis infection | 0.001085767 | 4 | 0 | BeFree |
| Fanconi Anemia | 0.000814326 | 3 | 0 | BeFree |
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