Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break
| العنوان: | Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break |
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| المؤلفون: | Katarzyna Bebenek, Andrea M. Kaminski, John M. Pryor, Thomas A. Kunkel, Dale A. Ramsden, Lars C. Pedersen |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020) Nature Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, DNA End-Joining Repair, DNA Repair, Protein Conformation, DNA damage, DNA repair, Science, General Physics and Astronomy, DNA-Directed DNA Polymerase, Crystallography, X-Ray, Article, General Biochemistry, Genetics and Molecular Biology, DNA Ligase ATP, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Humans, DNA Breaks, Double-Stranded, lcsh:Science, Polymerase, X-ray crystallography, chemistry.chemical_classification, DNA ligase, Multidisciplinary, biology, Synapsis, Hydrogen Bonding, DNA, General Chemistry, Cell biology, DNA-Binding Proteins, enzymes and coenzymes (carbohydrates), 030104 developmental biology, chemistry, Coding strand, biology.protein, lcsh:Q, 030217 neurology & neurosurgery, DNA Damage |
| الوصف: | Genomic integrity is threatened by cytotoxic DNA double-strand breaks (DSBs), which must be resolved efficiently to prevent sequence loss, chromosomal rearrangements/translocations, or cell death. Polymerase μ (Polμ) participates in DSB repair via the nonhomologous end-joining (NHEJ) pathway, by filling small sequence gaps in broken ends to create substrates ultimately ligatable by DNA Ligase IV. Here we present structures of human Polμ engaging a DSB substrate. Synapsis is mediated solely by Polμ, facilitated by single-nucleotide homology at the break site, wherein both ends of the discontinuous template strand are stabilized by a hydrogen bonding network. The active site in the quaternary Pol μ complex is poised for catalysis and nucleotide incoporation proceeds in crystallo. These structures demonstrate that Polμ may address complementary DSB substrates during NHEJ in a manner indistinguishable from single-strand breaks. Polymerase μ (Polμ) participates in the repair of DNA double-strand breaks (DSBs) via the nonhomologous end-joining (NHEJ) pathway. Here, the authors determine the crystal structure of a pre-catalytic ternary complex of human Polμ with a bound DSB substrate and they obtain further mechanistic insights by allowing the insertion reaction to proceed in crystallo, which enabled them to determine a Polμ structure with incomplete incorporation and the structure of the post-catalytic nicked state. |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e0e488bf693645fde3468c4b56b0e812 https://doi.org/10.1038/s41467-020-18506-5 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e0e488bf693645fde3468c4b56b0e812 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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