RAD18是RAD基因家族的重要成员,属于E3泛素连接酶家族,在DNA损伤修复和基因组稳定性维持中发挥关键作用。它的主要功能是通过泛素化修饰调控DNA损伤应答,特别是针对复制压力或紫外线等诱发的DNA损伤。RAD18与RAD6形成复合物,共同参与复制后修复(PRR)途径,通过单泛素化修饰PCNA(增殖细胞核抗原)来启动跨损伤DNA合成(TLS),允许DNA聚合酶绕过损伤位点继续复制。该基因在细胞核内活跃表达,尤其在快速增殖的细胞中表达较高。RAD18突变会导致DNA修复缺陷,增加基因组不稳定性,与多种癌症(如乳腺癌、卵巢癌和结直肠癌)的发生发展密切相关。突变可能削弱其与RAD6或PCNA的相互作用,损害TLS功能,导致突变积累和肿瘤易感性增加。RAD18过表达可能异常激活DNA损伤修复通路,促进癌细胞存活和化疗耐药;而表达降低则会导致DNA损伤修复能力下降,加剧基因组不稳定性。RAD18还参与调控同源重组(HR)和非同源末端连接(NHEJ)等其他修复途径,影响细胞周期检查点激活。RAD基因家族成员多参与DNA损伤应答,具有保守的锌指结构域或环指结构域,介导蛋白质相互作用和泛素化修饰。该家族在维持基因组完整性方面具有共性,但各成员在具体修复通路中的作用存在分工。
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Subcellular localization of RAD18 (and its protein):
Gene Ontology (GO) terms for RAD18:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| DNA Damage Bypass |
| DNA Repair |
| Recognition of DNA damage by PCNA-containing replication complex |
| Disease | Score | NofPmids | NofSnps | Source |
| Colorectal Cancer | 0.002909916 | 2 | 0 | BeFree_GAD |
| Colorectal Neoplasms | 0.00272435 | 1 | 0 | LHGDN |
| Lung Neoplasms | 0.00272435 | 1 | 0 | LHGDN |
| Malignant neoplasm of breast | 0.002367032 | 1 | 0 | GAD |
| Malignant neoplasm of lung | 0.002367032 | 1 | 0 | GAD |
| FANCONI ANEMIA, COMPLEMENTATION GROUP A (disorder) | 0.000814326 | 3 | 0 | BeFree |
| Fanconi Anemia | 0.000814326 | 3 | 0 | BeFree |
| Colorectal Carcinoma | 0.000542884 | 2 | 0 | BeFree |
| Non-Small Cell Lung Carcinoma | 0.000542884 | 2 | 2 | BeFree |
| Adenocarcinoma | 0.000271442 | 1 | 0 | BeFree |
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