The RING-type E3 ubiquitin ligases RNF8 and RNF168 recruit DNA damage response (DDR) factors to chromatin flanking DNA double strand breaks (DSBs) including 53BP1, which protects DNA ends from resection during DNA DSB repair by non-homologous end joining (NHEJ). Deficiency of RNF8 or RNF168 does not lead to demonstrable NHEJ defects, but like deficiency of 53BP1, the combined deficiency of XLF and RNF8 or RNF168 leads to diminished NHEJ in lymphocytes arrested in G₀/G₁ phase. The function of RNF8 in NHEJ depends on its E3 ubiquitin ligase activity. Loss of RNF8 or RNF168 in G₀/G₁-phase lymphocytes leads to the resection of broken DNA ends, demonstrating that RNF8 and RNF168 function to protect DNA ends from nucleases, pos sibly through the recruitment of 53BP1. However, the loss of 53BP1 leads to more severe resection than the loss of RNF8 or RNF168. Moreover, in 53BP1-deficient cells, the loss of RNF8 or RNF168 leads to diminished DNA end resection. We conclude that RNF8 and RNF168 regulate pathways that both prevent and promote DNA end resection in cells arrested in G₀/G₁ phase.

RING 型 E3 泛素连接酶 RNF8 和 RNF168 将 DNA 损伤反应 (DDR) 因子募集到染色质侧翼 DNA 双链断裂 (DSB) 中，包括 53BP1，通过非同源末端连接 (NHEJ) 在 DNA DSB 修复过程中保护 DNA 末端不被切除. RNF8 或 RNF168 的缺乏不会导致明显的 NHEJ 缺陷，但与 53BP1 的缺乏一样，XLF 和 RNF8 或 RNF168 的联合缺乏导致在 G ₀ /G ₁期停滞的淋巴细胞的 NHEJ 减少。NHEJ 中 RNF8 的功能取决于其 E3 泛素连接酶活性。_{G 0} /G ₁中 RNF8 或 RNF168 丢失期淋巴细胞导致断裂的 DNA 末端切除，证明 RNF8 和 RNF168 可保护 DNA 末端免受核酸酶的影响，可能通过募集 53BP1。然而，53BP1 的缺失导致比 RNF8 或 RNF168 的缺失更严重的切除。此外，在 53BP1 缺陷细胞中，RNF8 或 RNF168 的缺失导致 DNA 末端切除减少。_{我们得出结论，RNF8 和 RNF168 调节在 G 0} /G ₁期停滞的细胞中预防和促进 DNA 末端切除的途径。