ArticleThe EMBO journal2024
TDP1 phosphorylation by CDK1 in mitosis promotes MUS81-dependent repair of trapped Top1-DNA covalent complexes.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Solvent-controlled Rh-catalysed hydrodehalogenation and construction of phenanthridinone skeleton from a common precursor in one-step sequence and the antitumor activity of its derivatives.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation.Nucleic acids research · 2026Article
- Epitranscriptomic RNA editing resolves Mus81 DNA repair tradeoffs in heat tolerance and meiosis.Nature communications · 2026Article
- PRMT5 in mitochondria regulates mtDNA stability through TFAM arginine methylation.Nature communications · 2026Article
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
- Targeting TDP1 phosphorylation by the natural product imperatorin promotes DNA repair and cardiac regeneration.Communications biology · 2025Article
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Topoisomerase 1 (Top1) controls DNA topology, relieves DNA supercoiling during replication and transcription, and is critical for mitotic progression to the G1 phase. Tyrosyl-DNA phosphodiesterase 1 (TDP1) mediates the removal of trapped Top1-DNA covalent complexes (Top1cc). Here, we identify CDK1-dependent phosphorylation of TDP1 at residue S61 during mitosis. A TDP1 variant defective for S61 phosphorylation (TDP1-S61A) is trapped on the mitotic chromosomes, triggering DNA damage and mitotic defects. Moreover, we show that Top1cc repair in mitosis occurs via a MUS81-dependent DNA repair mechanism. Replication stress induced by camptothecin or aphidicolin leads to TDP1-S61A enrichment at common fragile sites, which over-stimulates MUS81-dependent chromatid breaks, anaphase bridges, and micronuclei, ultimately culminating in the formation of 53BP1 nuclear bodies during G1 phase. Our findings provide new insights into the cell cycle-dependent regulation of TDP1 dynamics for the repair of trapped Top1-DNA covalent complexes during mitosis that prevents genomic instability following replication stress.
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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 Socratic graph.