斯巴达/C1orf124，PCNA 泛素化的阅读器和 UV 诱导的 DNA 损伤反应的调节剂。
Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response.
机构信息
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
出版信息
Mol Cell. 2012 Jun 8;46(5):625-35. doi: 10.1016/j.molcel.2012.05.020.
PCNA is a key component of DNA replication and repair machineries. DNA damage-induced PCNA ubiquitylation serves as a molecular mark to orchestrate postreplication repair. Here, we have identified and characterized Spartan, a protein that specifically recognizes ubiquitylated PCNA and plays an important role in cellular resistance to UV radiation. In vitro, Spartan engages ubiquitylated PCNA via both a PIP box and a UBZ domain. In cells, Spartan is recruited to sites of UV damage in a manner dependent upon the PIP box, the UBZ domain, and PCNA ubiquitylation. Furthermore, Spartan colocalizes and interacts with Rad18, the E3 ubiquitin ligase that modifies PCNA. Surprisingly, while Spartan is recruited by ubiquitylated PCNA, knockdown of Spartan compromised chromatin association of Rad18, monoubiquitylation of PCNA, and localization of Pol η to UV damage. Thus, as a "reader" of ubiquitylated PCNA, Spartan promotes an unexpected feed-forward loop to enhance PCNA ubiquitylation and translesion DNA synthesis.
PCNA 是 DNA 复制和修复机制的关键组成部分。DNA 损伤诱导的 PCNA 泛素化作为一种分子标记，协调复制后修复。在这里，我们鉴定并描述了 Spartan，一种特异性识别泛素化 PCNA 的蛋白质，它在细胞对紫外线辐射的抗性中发挥着重要作用。在体外，Spartan 通过 PIP 盒和 UBZ 结构域与泛素化的 PCNA 结合。在细胞中，Spartan 以依赖于 PIP 盒、UBZ 结构域和 PCNA 泛素化的方式被招募到 UV 损伤部位。此外，Spartan 与 Rad18 共定位并相互作用，Rad18 是修饰 PCNA 的 E3 泛素连接酶。令人惊讶的是，虽然 Spartan 被泛素化的 PCNA 招募，但 Spartan 的敲低削弱了 Rad18 与染色质的结合、PCNA 的单泛素化以及 Pol η 对 UV 损伤的定位。因此，作为泛素化 PCNA 的“读取器”，Spartan 促进了一个意想不到的正反馈回路，以增强 PCNA 泛素化和跨损伤 DNA 合成。
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