ArticleProceedings of the National Academy of Sciences of the United States of America2009
Limited terminal transferase in human DNA polymerase mu defines the required balance between accuracy and efficiency in NHEJ.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Aspergillus fumigatus PolX1 is an early ancestor of vertebrate terminal deoxynucleotidyl transferases.Nucleic acids research · 2026Article
- Single-molecule techniques in studying the molecular mechanisms of DNA synapsis in non-homologous end-joining repair.Biophysics reports · 2025Article
- A mobile genetic element-derived primase-polymerase harbors multiple activities implicated in DNA replication and repair.Nucleic acids research · 2025Article
- Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation.Science China. Life sciences · 2024Review
- Targeting the DNA Damage Response and DNA Repair Pathways to Enhance Radiosensitivity in Colorectal Cancer.Cancers · 2022Review
- Mechanism of protein-primed template-independent DNA synthesis by Abi polymerases.Nucleic acids research · 2022Article
- Insight into the mechanism of DNA synthesis by human terminal deoxynucleotidyltransferase.Life science alliance · 2022Article
- Nuclear Actin Dynamics in Gene Expression, DNA Repair, and Cancer.Results and problems in cell differentiation · 2022Article
- Mechanism of genome instability mediated by human DNA polymerase mu misincorporation.Nature communications · 2021Article
- The molecular basis and disease relevance of non-homologous DNA end joining.Nature reviews. Molecular cell biology · 2020Review
- DNA polymerase mu: An inflexible scaffold for substrate flexibility.DNA repair · 2020Review
- Polymerase μ in non-homologous DNA end joining: importance of the order of arrival at a double-strand break in a purified system.Nucleic acids research · 2020Article
- Structural evidence for an inThe Journal of biological chemistry · 2019Article
- A versatile method for the UVA-induced cross-linking of acetophenone- or benzophenone-functionalized DNA.Scientific reports · 2018Article
- Enzymatic synthesis of random sequences of RNA and RNA analogues by DNA polymerase theta mutants for the generation of aptamer libraries.Nucleic acids research · 2018Article
- Primer-Independent DNA Synthesis by a Family B DNA Polymerase from Self-Replicating Mobile Genetic Elements.Cell reports · 2017Article
- Polμ tumor variants decrease the efficiency and accuracy of NHEJ.Nucleic acids research · 2017Article
- Article
- Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell.Chemical reviews · 2016Review
- ATP insertion opposite 8-oxo-deoxyguanosine by Pol4 mediates error-free tolerance in Schizosaccharomyces pombe.Nucleic acids research · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA polymerase mu (Polmu) is a family X member implicated in DNA repair, with template-directed and terminal transferase (template-independent) activities. It has been proposed that the terminal transferase activity of Polmu can be specifically required during non-homologous end joining (NHEJ) to create or increase complementarity of DNA ends. By site-directed mutagenesis in human Polmu, we have identified a specific DNA ligand residue (Arg(387)) that is responsible for its limited terminal transferase activity compared to that of human TdT, its closest homologue (42% amino acid identity). Polmu mutant R387K (mimicking TdT) displayed a large increase in terminal transferase activity, but a weakened interaction with ssDNA. That paradox can be explained by the regulatory role of Arg(387) in the translocation of the primer from a non-productive E:DNA complex to a productive E:DNA:dNTP complex in the absence of a templating base, which is probably the rate limiting step during template-independent synthesis. Further, we show that the Polmu switch from terminal transferase to templated insertions in NHEJ reactions is triggered by recognition of a 5'-P at a second DNA end, whose 3'-protrusion could provide a templating base to facilitate such a special "pre-catalytic translocation step." These studies shed light on the mechanism by which a rate-limited terminal transferase activity in Polmu could regulate the balance between accuracy and necessary efficiency, providing some variability during NHEJ.
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