Authophagy and G2/M arrest are two important mechanistic responses of cells to ionizing radiation (IR), in particular the IR-induced fibrosis. However, what interplayer and how it links the autophagy and the G₂/M arrest remains elusive. Here, we demonstrate that the autophagy-related protein BECN1 plays a critical role in ionizing radiation-induced G₂/M arrest. The treatment of cells with autophagy inhibitor 3-methyladenine (3-MA) at 0–12 h but not 12 h postirradiation significantly sensitized them to IR, indicating a radio-protective role of autophagy in the early response of cells to radiation. 3-MA and BECN1 disruption inactivated the G₂/M checkpoint following IR by abrogating the IR-induced phosphorylation of phosphatase CDC25C and its target CDK1, a key mediator of the G₂/M transition in coordination with CCNB1. Irradiation increased the nuclear translocation of BECN1, and this process was inhibited by 3-MA. We confirmed that BECN1 interacts with CDC25C and CHK2, and which is mediated the amino acids 89–155 and 151–224 of BECN1, respectively. Importantly, BECN1 deficiency disrupted the interaction of CHK2 with CDC25C and the dissociation of CDC25C from CDK1 in response to irradiation, resulting in the dephosphorylation of CDK1 and overexpression of CDK1. In summary, IR induces the translocation of BECN1 to the nucleus, where it mediates the interaction between CDC25C and CHK2, resulting in the phosphorylation of CDC25C and its dissociation from CDK1. Consequently, the mitosis-promoting complex CDK1/CCNB1 is inactivated, resulting in the arrest of cells at the G₂/M transition. Our findings demonstrated that BECN1 plays a role in promotion of radiation-induced G2/M arrest through regulation of CDK1 activity. Whether such functions of BECN1 in G2/M arrest is dependent or independent on its autophagy-related roles is necessary to further identify.

自噬和 G2/M 期停滞是细胞对电离辐射 (IR)，特别是 IR 诱导的纤维化的两种重要机制反应。然而，什么相互作用以及它如何将自噬与 G ₂ /M 逮捕联系起来仍然难以捉摸。在这里，我们证明自噬相关蛋白 BECN1 在电离辐射诱导的 G ₂ /M 阻滞中发挥着关键作用。在辐射后 0-12 小时而非 12 小时用自噬抑制剂 3-甲基腺嘌呤 (3-MA) 处理细胞，可显着使细胞对 IR 敏感，表明自噬在细胞对辐射的早期反应中具有辐射防护作用。3-MA 和 BECN1 破坏通过消除 IR 诱导的磷酸酶 CDC25C 及其靶标 CDK1（与CCNB1 协调的G _{2 /M 转变的关键介质）磷酸化，使 IR 后的 G 2 /M 检查点失活。}辐射增加了 BECN1 的核转位，而该过程被 3-MA 抑制。我们证实BECN1与CDC25C和CHK2相互作用，并且分别介导BECN1的氨基酸89-155和151-224。重要的是，BECN1 缺陷破坏了 CHK2 与 CDC25C 的相互作用以及 CDC25C 在辐射反应中与 CDK1 的解离，导致 CDK1 去磷酸化和 CDK1 过度表达。总之，IR 诱导 BECN1 易位至细胞核，在细胞核中介导 CDC25C 和 CHK2 之间的相互作用，导致 CDC25C 磷酸化及其与 CDK1 的解离。_{因此，促进有丝分裂的复合物 CDK1/CCNB1 失活，导致细胞在 G 2} /M 转变时停滞。我们的研究结果表明，BECN1 通过调节 CDK1 活性在促进辐射诱导的 G2/M 期停滞中发挥作用。BECN1 在 G2/M 期停滞中的这种功能是否依赖于或独立于其自噬相关作用，有必要进一步确定。