The cullin Rtt101 promotes ubiquitin-dependent DNA-Protein Crosslink repair across the cell cycle

DNA‒protein crosslinks (DPCs) challenge faithful DNA replication and fluid passage of genomic information. Our study unveils the cullin ubiquitin ligase Rtt101 as a novel DPC repair factor. Genetic analyses demonstrate that Rtt101 is essential for resistance to a wide range of DPC types. Using an inducible in vivo DPC system, we reveal the significant impact of Rtt101 on DPC removal, including topoisomerase 1 crosslinks. ChIP-sequencing and ChEC-sequencing specifically highlight the association of Rtt101 with replisomes as well as colocalization with DPCs. Our findings establish Rtt101 as a novel main contributor to DPC repair throughout the yeast cell cycle.DNA-蛋白质交联（DNA-protein crosslinks, DPCs）会干扰DNA的忠实复制与基因组信息的精准传递。本研究揭示cullin泛素连接酶（cullin ubiquitin ligase）Rtt101是一类新型DPC修复因子。遗传分析表明，Rtt101对于耐受多种类型DPC至关重要。利用诱导型体内DPC模型，我们证实Rtt101可显著促进包括拓扑异构酶1（topoisomerase 1）交联在内的各类DPC的清除。染色质免疫沉淀测序（ChIP-sequencing）与染色质内切酶制图测序（ChEC-sequencing）结果特异性显示，Rtt101可与复制体（replisomes）结合，并与DPC发生共定位。本研究结果确立Rtt101作为酵母细胞周期中DPC修复的新型核心贡献因子。