ArticleNucleic acids research2019
A genome-wide RNAi screen identifies the SMC5/6 complex as a non-redundant regulator of a Topo2a-dependent G2 arrest.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Ligase-dependent and independent functions of the C-terminus of Mms21 contribute to optimal growth and genome stability inMolecular biology of the cell · 2026Article
- Copper Complexes: Main Mechanisms as Anticancer Agents.Molecules (Basel, Switzerland) · 2026Review
- Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication.Virologica Sinica · 2025Article
- TOP2A inhibition and its cellular effects related to cell cycle checkpoint adaptation pathway.Scientific reports · 2025Article
- Inhibition of topoisomerase 2 catalytic activity impacts the integrity of heterochromatin and repetitive DNA and leads to interlinks between clustered repeats.Nature communications · 2024Article
- On the Prevalence and Roles of Proteins Undergoing Liquid-Liquid Phase Separation in the Biogenesis of PML-Bodies.Biomolecules · 2023Article
- Cell cycle responses to Topoisomerase II inhibition: Molecular mechanisms and clinical implications.The Journal of cell biology · 2023Review
- Genome control by SMC complexes.Nature reviews. Molecular cell biology · 2023Review
- The SUMO-NIP45 pathway processes toxic DNA catenanes to prevent mitotic failure.Nature structural & molecular biology · 2023Article
- Regulation of the mitotic chromosome folding machines.The Biochemical journal · 2022Article
- NSMCE2, a novel super-enhancer-regulated gene, is linked to poor prognosis and therapy resistance in breast cancer.BMC cancer · 2022Article
- KSHV RTA antagonizes SMC5/6 complex-induced viral chromatin compaction by hijacking the ubiquitin-proteasome system.PLoS pathogens · 2022Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Genome-Protective Topoisomerase 2a-Dependent G2 Arrest Requires p53 in hTERT-Positive Cancer Cells.Cancer research · 2022Article
- A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division.Nature communications · 2021Article
- Equivocal, explicit and emergent actions of PKC isoforms in cancer.Nature reviews. Cancer · 2021Review
- Purified Smc5/6 Complex Exhibits DNA Substrate Recognition and Compaction.Molecular cell · 2020Article
- A cancer-associated, genome protective programme engaging PKCε.Advances in biological regulation · 2020Review
- Mitotic entry upon Topo II catalytic inhibition is controlled by Chk1 and Plk1.The FEBS journal · 2020Article
- Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The Topo2a-dependent arrest is associated with faithful segregation of sister chromatids and has been identified as dysfunctional in numerous tumour cell lines. This genome-protecting pathway is poorly understood and its characterization is of significant interest, potentially offering interventional opportunities in relation to synthetic lethal behaviours in arrest-defective tumours. Using the catalytic Topo2a inhibitor ICRF193, we have performed a genome-wide siRNA screen in arrest-competent, non-transformed cells, to identify genes essential for this arrest mechanism. In addition, we have counter-screened several DNA-damaging agents and demonstrate that the Topo2a-dependent arrest is genetically distinct from DNA damage checkpoints. We identify the components of the SMC5/6 complex, including the activity of the E3 SUMO ligase NSE2, as non-redundant players that control the timing of the Topo2a-dependent arrest in G2. We have independently verified the NSE2 requirement in fibroblasts from patients with germline mutations that cause severely reduced levels of NSE2. Through imaging Topo2a-dependent G2 arrested cells, an increased interaction between Topo2a and NSE2 is observed at PML bodies, which are known SUMOylation hotspots. We demonstrate that Topo2a is SUMOylated in an ICRF193-dependent manner by NSE2 at a novel non-canonical site (K1520) and that K1520 sumoylation is required for chromosome segregation but not the G2 arrest.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.