ArticlePLoS genetics2017
Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Interfering with DNA repair pathways to enhance CRISPR-Cas9-mediated homology-directed repair in a chelicerate genetic model.iScience · 2026Article
- Activation of Pol theta-mediated end joining begins during mitotic commitment.bioRxiv : the preprint server for biology · 2026Article
- Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- The relationship between DNA damage and repair and the occurrence and development of disease.Frontiers in genetics · 2026Review
- Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Suppression of plastid-to-nucleus gene transfer by DNA double-strand break repair.Nature plants · 2025Article
- Division of labor within polymerase theta in repair of CRISPR-induced DNA breaks inPNAS nexus · 2025Article
- A non-tethering role for the Drosophila Pol θ linker domain in promoting damage resolution.Nucleic acids research · 2025Article
- PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks.Nature communications · 2024Article
- Sequential requirements for distinct Polθ domains during theta-mediated end joining.Molecular cell · 2024Article
- Clinical and translational advances in ovarian cancer therapy.Nature cancer · 2023Review
- Article
- Fanconi anemia-associated chromosomal radial formation is dependent on POLθ-mediated alternative end joining.Cell reports · 2023Article
- DNA polymerase θ-mediated repair of high LET radiation-induced complex DNA double-strand breaks.Nucleic acids research · 2023Article
- Genome Protection by DNA Polymerase θ.Annual review of genetics · 2022Review
- Article
- Review
- Characterization of sequence contexts that favor alternative end joining at Cas9-induced double-strand breaks.Nucleic acids research · 2022Article
- Synthetic Lethality Targeting Polθ.Genes · 2022Review
- Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining.Nature reviews. Molecular cell biology · 2022Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase θ (Pol θ), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol θ contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol θ. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol θ can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol θ and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance.
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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.