ArticleNucleic acids research2012
DNA-binding determinants promoting NHEJ by human Polμ.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- 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
- Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break.Nature communications · 2020Article
- 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
- Exonuclease 1 (Exo1) Participates in Mammalian Non-Homologous End Joining and Contributes to Drug Resistance in Ovarian Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Structure and function relationships in mammalian DNA polymerases.Cellular and molecular life sciences : CMLS · 2020Review
- Copy Number Amplification of DNA Damage Repair Pathways Potentiates Therapeutic Resistance in Cancer.Theranostics · 2020Article
- Polμ tumor variants decrease the efficiency and accuracy of NHEJ.Nucleic acids research · 2017Article
- Creative template-dependent synthesis by human polymerase mu.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Structural basis for a novel mechanism of DNA bridging and alignment in eukaryotic DSB DNA repair.The EMBO journal · 2015Article
- Decision-making during NHEJ: a network of interactions in human Polμ implicated in substrate recognition and end-bridging.Nucleic acids research · 2014Article
- Sustained active site rigidity during synthesis by human DNA polymerase μ.Nature structural & molecular biology · 2014Article
- Molecular basis for DNA double-strand break annealing and primer extension by an NHEJ DNA polymerase.Cell reports · 2013Article
- A specific N-terminal extension of the 8 kDa domain is required for DNA end-bridging by human Polμ and Polλ.Nucleic acids research · 2013Article
- Repair of double-strand breaks by end joining.Cold Spring Harbor perspectives in biology · 2013Review
- DNA expansions generated by human Polμ on iterative sequences.Nucleic acids research · 2013Article
- Yeast pol4 promotes tel1-regulated chromosomal translocations.PLoS genetics · 2013Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-homologous end-joining (NHEJ), the preferred pathway to repair double-strand breaks (DSBs) in higher eukaryotes, relies on a collection of molecular tools to process the broken ends, including specific DNA polymerases. Among them, Polµ is unique as it can catalyze DNA synthesis upon connection of two non-complementary ends. Here, we demonstrate that this capacity is intrinsic to Polµ, not conferred by other NHEJ factors. To understand the molecular determinants of its specific function in NHEJ, the interaction of human Polµ with DNA has been directly visualized by electromobility shift assay and footprinting assays. Stable interaction with a DNA gap requires the presence of a recessive 5'-P, thus orienting the catalytic domain for primer and nucleotide binding. Accordingly, recognition of the 5'-P is crucial to align the two DNA substrates of the NHEJ reaction. Site-directed mutagenesis demonstrates the relevance of three specific residues (Lys(249), Arg(253) and Arg(416)) in stabilizing the primer strand during end synapsis, allowing a range of microhomology-induced distortions beneficial for NHEJ. Moreover, our results suggest that the Polµ BRCT domain, thought to be exclusively involved in interaction with NHEJ core factors, has a direct role in binding the DNA region neighbor to the 5'-P, thus boosting Polµ-mediated NHEJ reactions.
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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.