ArticleProceedings of the National Academy of Sciences of the United States of America2015
Essential role for polymerase specialization in cellular nonhomologous end joining.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed.
- Nonhomologous end-joining uses distinct mechanisms to repair each strand of a double strand break.Nature communications · 2025Article
- Article
- Structural and functional insights into the interaction between Ku70/80 and Pol X family polymerases in NHEJ.Nature communications · 2025Article
- The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations.Nature communications · 2024Article
- DNA repair and anti-cancer mechanisms in the long-lived bowhead whale.bioRxiv : the preprint server for biology · 2024Article
- The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations.bioRxiv : the preprint server for biology · 2024Article
- DNA polymerase λ Loop1 variant yields unexpected gain-of-function capabilities in nonhomologous end-joining.DNA repair · 2024Article
- Current Strategies for Increasing Knock-In Efficiency in CRISPR/Cas9-Based Approaches.International journal of molecular sciences · 2024Review
- For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases.International journal of molecular sciences · 2023Review
- Review
- Diversity upon diversity: linking DNA double-strand break repair to blood cancer health disparities.Trends in cancer · 2022Review
- Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining.Nature reviews. Molecular cell biology · 2022Review
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
- Review
- Repair of DNA Double-Strand Breaks by the Nonhomologous End Joining Pathway.Annual review of biochemistry · 2021Review
- Ku70 suppresses alternative end joining in G1-arrested progenitor B cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A novel role of DNA polymerase λ in translesion synthesis in conjunction with DNA polymerase ζ.Life science alliance · 2021Article
- The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides.Scientific reports · 2021Article
- The molecular basis and disease relevance of non-homologous DNA end joining.Nature reviews. Molecular cell biology · 2020Review
- Polymerase δ promotes chromosomal rearrangements and imprecise double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Nonhomologous end joining (NHEJ) repairs chromosome breaks and must remain effective in the face of extensive diversity in broken end structures. We show here that this flexibility is often reliant on the ability to direct DNA synthesis across strand breaks, and that polymerase (Pol) μ and Pol λ are the only mammalian DNA polymerases that have this activity. By systematically varying substrate in cells, we show each polymerase is uniquely proficient in different contexts. The templating nucleotide is also selected differently, with Pol μ using the unpaired base adjacent to the downstream 5' phosphate even when there are available template sites further upstream of this position; this makes Pol μ more flexible but also less accurate than Pol λ. Loss of either polymerase alone consequently has clear and distinguishable effects on the fidelity of repair, but end remodeling by cellular nucleases and the remaining polymerase helps mitigate the effects on overall repair efficiency. Accordingly, when cells are deficient in both polymerases there is synergistic impact on NHEJ efficiency, both in terms of repair of defined substrates and cellular resistance to ionizing radiation. Pol μ and Pol λ thus provide distinct solutions to a problem for DNA synthesis that is unique to this pathway and play a key role in conferring on NHEJ the flexibility required for accurate and efficient repair.
Indexed as
Identifiers
What OpenQuestion holds
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.