RAD17（也称为RAD17 homolog或hRAD17）是一个重要的细胞周期检查点调控基因，属于RAD基因家族，该家族主要参与DNA损伤修复和细胞周期调控。RAD17基因编码的蛋白质是一种检查点蛋白，它在DNA损伤应答（DDR）中起关键作用，特别是在激活ATR（共济失调毛细血管扩张症和Rad3相关蛋白）信号通路时。RAD17蛋白与RFC（复制因子C）复合物类似，能够结合DNA损伤位点并招募其他检查点蛋白（如RAD9、HUS1和RAD1组成的9-1-1复合物），从而启动细胞周期阻滞以允许DNA修复。RAD17的主要作用位点包括DNA损伤位点和复制叉，它通过监测DNA完整性来确保基因组稳定性。突变或功能缺失的RAD17会导致DNA损伤修复缺陷，增加基因组不稳定性，进而可能引发癌症（如乳腺癌、卵巢癌和结直肠癌）或对放疗和化疗的敏感性改变。此外，RAD17的某些突变还与遗传性疾病（如早衰综合征）相关。如果RAD17过表达，可能增强细胞对DNA损伤的敏感性，导致过度激活的检查点反应和细胞周期停滞，甚至细胞凋亡；而降低表达则可能导致DNA损伤积累，增加突变率和肿瘤发生风险。RAD17与其他检查点蛋白（如ATR、CHK1和p53）相互作用，共同维持基因组稳定性。RAD基因家族的共性在于它们均参与DNA损伤修复和细胞周期调控，许多成员（如RAD51、RAD52）在重组修复中发挥作用，而RAD17则更侧重于检查点激活。该家族的基因通常对维持细胞稳态和防止癌变至关重要。

由该基因编码的蛋白质是高度相似裂殖酵母RAD17，响应于DNA损伤细胞周期停滞和DNA损伤修复所需的细胞周期检查点基因的基因产物。这种蛋白与DNA复制因子C（RFC）较强的相似性，并能形成的RFC复杂。该蛋白质结合之前对DNA损伤染色质，并通过以下损坏检查点激酶ATR磷酸化。这种蛋白募集的DNA损伤，这可能需要它的磷酸化后RAD1-RAD9-HUS1关卡蛋白复合物上的染色质。该蛋白质的磷酸化是必需的DNA损伤诱导的细胞周期G2期阻滞，并且被认为是在DNA的受损细胞的检查点信号中一个关键的早期事件。 ，已经报道了这个基因的多个可变剪接转录物变体，其编码四种不同的蛋白质同种型。两个假，位于染色体7和13，也已确定。 [由RefSeq的，2013年7月提供]

RAD17, also known as RAD17 homolog or hRAD17, is a critical regulator of cell cycle checkpoints that belongs to the RAD gene family, a group of genes predominantly involved in DNA damage repair and cell cycle control. The protein encoded by RAD17 functions as a key checkpoint effector within the DNA damage response (DDR), playing a pivotal role in the activation of the ataxia telangiectasia and Rad3-related protein (ATR) signaling pathway. Structurally and functionally analogous to the Replication Factor C (RFC) complex, RAD17 localizes to sites of DNA damage and replication forks, where it recruits the 9-1-1 complex—composed of RAD9, HUS1, and RAD1—to initiate cell cycle arrest and facilitate DNA repair. By continuously monitoring DNA integrity, RAD17 ensures genomic stability and coordinates with other checkpoint proteins, including ATR, CHK1, and p53, to maintain cellular homeostasis. Disruption of RAD17 function, whether through mutation or loss, compromises DNA damage repair mechanisms, leading to increased genomic instability and an elevated risk of malignancies such as breast, ovarian, and colorectal cancers, as well as altered sensitivity to radiotherapy and chemotherapy. Conversely, overexpression of RAD17 can paradoxically enhance cellular sensitivity to DNA damage by triggering excessive checkpoint activation, resulting in prolonged cell cycle arrest or apoptosis, while reduced expression promotes the accumulation of DNA lesions and mutagenesis. Although many members of the RAD family, such as RAD51 and RAD52, are primarily involved in homologous recombination repair, RAD17 is distinguished by its specific emphasis on checkpoint activation, and certain mutations in this gene have also been linked to hereditary conditions, including progeria syndromes, underscoring its essential role in preventing cancer and maintaining overall cellular integrity.

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