ArticleProceedings of the National Academy of Sciences of the United States of America2025
Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- DNA Repair Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Microhomology-mediated end joining acts directly on replication forks to repair single-ended double-strand breaks.Molecular cell · 2026Article
- Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
DNA polymerase theta (Pol θ)-mediated end joining (TMEJ) initiates DNA double-strand break repair by using short homologies (microhomologies) between single-stranded DNA tails. This repair process is particularly important in cancer cells defective in homologous recombination. The exonuclease function of DNA polymerase delta (Pol δ) has been identified as an essential component for TMEJ, functioning to remove unpaired bases flanking a microhomology (MH). It is not known if the exonuclease removes all unpaired bases at once and how this removal might affect subsequent MH selection. Here, we reconstituted a functional TMEJ repair process using purified human Pol θ and Pol δ. We find that when Pol δ exonuclease excises a nucleotide to generate a new 3' terminus, Pol θ initiates a new MH search. Pol δ exonuclease removes a single nucleotide at a time, rather than cleaving an unpaired flap, and then transfers the DNA tail to the polymerase site of Pol θ. Specific primer-grasp amino acids in the polymerase domain of Pol θ are important for internal MH anchoring. The helicase-like domain of Pol θ harbors two activities which are recapitulated in reconstituted reactions: strand-capture to bring single-strand tails together and an ATPase activity that alleviates suppression of TMEJ by ssDNA binding protein RPA. This functional reconstitution of TMEJ advances the understanding of how two polymerases with three enzymatic activities orchestrate double-strand break repair.
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Registered trials
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