The cullin Rtt101 promotes ubiquitin-dependent DNA−protein crosslink repair across the cell cycle

• Published in: Nucleic acids research 2024-09, Vol.52 (16), p.9654-9670
• Main Authors: Noireterre, Audrey, Soudet, Julien, Bagdiul, Ivona, Stutz, Françoise
• Format: Article
• Language: English
• Subjects: Cell Cycle - genetics; Cullin Proteins - genetics; Cullin Proteins - metabolism; DNA Damage; DNA Repair; DNA Replication; DNA Topoisomerases, Type I - genetics; DNA Topoisomerases, Type I - metabolism; DNA, Fungal - genetics; DNA, Fungal - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Genome Integrity, Repair and; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Ubiquitin - genetics; Ubiquitin - metabolism; Ubiquitination
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkae658

Abstract 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. Graphical Abstract Graphical Abstract