The cullin Rtt101 promotes ubiquitin-dependent DNA-protein crosslink repair across the cell cycle.
DNA-protein crosslinks (DPCs) challenge faithful DNA replication and smooth passage of genomic information. Our study unveils the cullin E3 ubiquitin ligase Rtt101 as a DPC repair factor. Genetic analyses demonstrate that Rtt101 is essential for resistance to a wide range of DPC types including topoisomerase 1 crosslinks, in the same ... pathway as the ubiquitin-dependent aspartic protease Ddi1. Using an in vivo inducible Top1-mimicking DPC system, we reveal the significant impact of Rtt101 ubiquitination on DPC removal across different cell cycle phases. High-throughput methods coupled with next-generation sequencing specifically highlight the association of Rtt101 with replisomes as well as colocalization with DPCs. Our findings establish Rtt101 as a main contributor to DPC repair throughout the yeast cell cycle.
Mesh Terms:
Cell Cycle, Cullin Proteins, DNA Adducts, DNA Repair, DNA Replication, DNA Topoisomerases, Type I, Multienzyme Complexes, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitination
Cell Cycle, Cullin Proteins, DNA Adducts, DNA Repair, DNA Replication, DNA Topoisomerases, Type I, Multienzyme Complexes, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitination
Nucleic Acids Res
Date: Sep. 09, 2024
PubMed ID: 39077933
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