ArticleNucleic acids research2013
DNA topoisomerase IIα controls replication origin cluster licensing and firing time in Xenopus egg extracts.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Topological stress regulates replication fork dynamics in unperturbed S phase.Nature communications · 2026Article
- Deciphering linezolid-induced hematologic toxicity: Targeting TOP2A and TOP2B via its primary metabolite PNU142586.Science advances · 2025Article
- Sperm derived H2AK119ub1 is required for embryonic development in Xenopus laevis.Nature communications · 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
- Rif1 restrains the rate of replication origin firing in Xenopus laevis.Communications biology · 2023Article
- Article
- Topoisomerase II poisons inhibit vertebrate DNA replication through distinct mechanisms.The EMBO journal · 2022Article
- Genome-Protective Topoisomerase 2a-Dependent G2 Arrest Requires p53 in hTERT-Positive Cancer Cells.Cancer research · 2022Article
- Epigenetic homogeneity in histone methylation underlies sperm programming for embryonic transcription.Nature communications · 2020Article
- Topoisomerase IIα prevents ultrafine anaphase bridges by two mechanisms.Open biology · 2020Article
- Review
- Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.Nature reviews. Molecular cell biology · 2016Review
- Sperm is epigenetically programmed to regulate gene transcription in embryos.Genome research · 2016Article
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Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sperm chromatin incubated in Xenopus egg extracts undergoes origin licensing and nuclear assembly before DNA replication. We found that depletion of DNA topoisomerase IIα (topo IIα), the sole topo II isozyme of eggs and its inhibition by ICRF-193, which clamps topo IIα around DNA have opposite effects on these processes. ICRF-193 slowed down replication origin cluster activation and fork progression in a checkpoint-independent manner, without altering replicon size. In contrast, topo IIα depletion accelerated origin cluster activation, and topo IIα add-back negated overinitiation. Therefore, topo IIα is not required for DNA replication, but topo IIα clamps slow replication, probably by forming roadblocks. ICRF-193 had no effect on DNA synthesis when added after nuclear assembly, confirming that topo IIα activity is dispensable for replication and revealing that topo IIα clamps formed on replicating DNA do not block replication, presumably because topo IIα acts behind and not in front of forks. Topo IIα depletion increased, and topo IIα addition reduced, chromatin loading of MCM2-7 replicative helicase, whereas ICRF-193 did not affect MCM2-7 loading. Therefore, topo IIα restrains MCM2-7 loading in an ICRF-193-resistant manner during origin licensing, suggesting a model for establishing the sequential firing of origin clusters.
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