Year: 2020
Type: preprint
Abstract: SUMMARY Several endogenous metabolites, environmental agents, and therapeutic drugs promote formation of covalent DNA-protein crosslinks (DPCs). Persistent DPCs pose a serious threat to genome integrity and are eliminated by multiple repair pathways. Aberrant Top1 crosslinks to DNA, or Top1ccs, are processed by Tdp1 and Wss1 functioning in parallel pathways in Saccharomyces cerevisiae. It remains obscure how cells choose between these diverse mechanisms of DPC repair. Here we show that several SUMO biogenesis factors - Ulp1, Siz2, Slx5, Slx8 - control repair of Top1cc or an analogous DPC lesion. Genetic analysis reveals that SUMO promotes Top1cc processing in the absence of Tdp1 but has an inhibitory role if cells additionally lack Wss1. In the tdp1Δ wss1Δ mutant, the E3 SUMO ligase Siz2 stimulates sumoylation in the vicinity of the DPC, but not SUMO conjugation to Top1. This Siz2-dependent sumoylation delays DPC repair when cells progress through S and G2 phases. Our findings suggest that SUMO tunes available repair pathways to facilitate faithful DPC repair.
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Interorganelle lipid exchange networks, G1088503213, G1776853677, Effect of yeast pervasive transcription on gene regulation and replication, and link between nuclear organization, sumoylation and resolution of DNA-protein covalent complexes, Molecular basis of lipid traffic at interorganelle contact sites, Contemporary Approaches to Cancer Cell Signaling and Communication, Molecular basis of lipid traffic at interorganelle contact sites, G544591541, G5520316217, G6517203713, G7518776069, Role of antisense transcription in gene regulation and importance of ubiquitination and sumoylation in mRNA biogenesis and export during yeast cell cycle progression., Orbitrap Fusion Mass Spectrometer, G9000043645, G9000060249, G9000144590
OpenAlex ID: W3032932146