ArticleCell reports2021
Polθ promotes the repair of 5'-DNA-protein crosslinks by microhomology-mediated end-joining.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 23 citations in OpenAlex.
- Suppression of transcription-replication conflicts by sequence-coordinated actions of TRDMT1 and MutLα.Nature communications · 2026Article
- Apoptosis-driven chromosomal rearrangements in cancer: CAD cleavage, nuclear architecture, and microhomology-mediated end joining.Oncogenesis · 2026Review
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- A fast-to-faithful transition shapes the DNA repair landscape during embryogenesis.bioRxiv : the preprint server for biology · 2026Article
- Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia.Cell reports. Medicine · 2026Article
- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors.Journal of medicinal chemistry · 2025Article
- Article
- Structural basis for a Polθ helicase small-molecule inhibitor revealed by cryo-EM.Nature communications · 2024Article
- PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks.Nature communications · 2024Article
- Discovery of a small-molecule inhibitor that traps Polθ on DNA and synergizes with PARP inhibitors.Nature communications · 2024Article
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription.Nature communications · 2023Article
- Article
- Multifaceted Nature of DNA Polymerase θ.International journal of molecular sciences · 2023Review
- Polλ promotes microhomology-mediated end-joining.Nature structural & molecular biology · 2023Article
- Genome Protection by DNA Polymerase θ.Annual review of genetics · 2022Review
- The contribution of DNA repair pathways to genome editing and evolution in filamentous pathogens.FEMS microbiology reviews · 2022Review
- Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining.Nature reviews. Molecular cell biology · 2022Review
- The repair of topoisomerase 2 cleavage complexes in Arabidopsis.The Plant cell · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
DNA polymerase θ (Polθ) confers resistance to chemotherapy agents that cause DNA-protein crosslinks (DPCs) at double-strand breaks (DSBs), such as topoisomerase inhibitors. This suggests Polθ might facilitate DPC repair by microhomology-mediated end-joining (MMEJ). Here, we investigate Polθ repair of DSBs carrying DPCs by monitoring MMEJ in Xenopus egg extracts. MMEJ in extracts is dependent on Polθ, exhibits the MMEJ repair signature, and efficiently repairs 5' terminal DPCs independently of non-homologous end-joining and the replisome. We demonstrate that Polθ promotes the repair of 5' terminal DPCs in mammalian cells by using an MMEJ reporter and find that Polθ confers resistance to formaldehyde in addition to topoisomerase inhibitors. Dual deficiency in Polθ and tyrosyl-DNA phosphodiesterase 2 (TDP2) causes severe cellular sensitivity to etoposide, which demonstrates MMEJ as an independent DPC repair pathway. These studies recapitulate MMEJ in vitro and elucidate how Polθ confers resistance to etoposide.
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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.