In Arabidopsis (Arabidopsis thaliana), the F-box protein F-BOX-LIKE17 (FBL17) was previously identified as an important cell-cycle regulatory protein. FBL17 is required for cell division during pollen development and for normal cell-cycle progression and endoreplication during the diploid sporophyte phase. FBL17 was reported to control the stability of the CYCLIN-DEPENDENT KINASE inhibitor KIP-RELATED PROTEIN (KRP), which may underlie the drastic reduction in cell division activity in both shoot and root apical meristems observed in fbl17 loss-of-function mutants. However, whether FBL17 has other substrates and functions besides degrading KRPs remains poorly understood. Here we show that mutation of FBL17 leads not only to misregulation of cell cycle genes, but also to a strong upregulation of genes involved in DNA damage and repair processes. This phenotype is associated with a higher frequency of DNA lesions in fbl17 and increased cell death in the root meristem, even in the absence of genotoxic stress. Notably, the constitutive activation of DNA damage response genes is largely SOG1-independent in fbl17. In addition, through analyses of root elongation, accumulation of cell death, and occurrence of H2AX foci, we found that fbl17 mutants are hypersensitive to DNA double-strand break-induced genotoxic stress. Notably, we observed that the FBL17 protein is recruited at nuclear foci upon double-strand break induction and colocalizes with H2AX, but only in the presence of RETINOBLASTOMA RELATED1. Altogether, our results highlight a role for FBL17 in DNA damage response, likely by ubiquitylating proteins involved in DNA-damage signaling or repair.

在拟南芥 ( Arabidopsis thaliana ) 中，F-box 蛋白 F-BOX-LIKE17 (FBL17) 先前被鉴定为重要的细胞周期调节蛋白。FBL17 是花粉发育过程中细胞分裂以及二倍体孢子体阶段正常细胞周期进程和内复制所必需的。据报道，FBL17 控制循环素依赖性激酶抑制剂 KIP 相关蛋白 (KRP) 的稳定性，这可能是在fbl17功能丧失突变体中观察到的地上部和根尖分生组织中细胞分裂活性急剧下降的基础。然而，除了降解 KRP 之外，FBL17 是否还有其他底物和功能仍然知之甚少。这里我们展示了FBL17 的突变不仅会导致细胞周期基因的错误调节，还会导致参与 DNA 损伤和修复过程的基因的强烈上调。这种表型与fbl17 中更高频率的 DNA 损伤和根分生组织中细胞死亡的增加有关，即使在没有遗传毒性应激的情况下也是如此。值得注意的是，DNA损伤应答基因的组成性活化在很大程度上SOG1无关在fbl17。此外，通过对根伸长、细胞死亡积累和 H2AX 病灶发生的分析，我们发现fbl17突变体对 DNA 双链断裂诱导的基因毒性应激高度敏感。值得注意的是，我们观察到 FBL17 蛋白在双链断裂诱导后在核病灶处募集并与 H2AX 共定位，但仅在存在视网膜母细胞瘤相关 1 的情况下。总而言之，我们的结果强调了 FBL17 在 DNA 损伤反应中的作用，可能是通过泛素化参与 DNA 损伤信号传导或修复的蛋白质。