In crystallo observation of three metal ion promoted DNA polymerase misincorporation
| dc.citation.articleNumber | 2346 | |
| dc.citation.journalTitle | Nature Communications | |
| dc.citation.volumeNumber | 13 | |
| dc.contributor.author | Chang, Caleb | |
| dc.contributor.author | Lee Luo, Christie | |
| dc.contributor.author | Gao, Yang | |
| dc.date.accessioned | 2022-05-25T17:37:46Z | |
| dc.date.available | 2022-05-25T17:37:46Z | |
| dc.date.issued | 2022 | |
| dc.description.abstract | Error-free replication of DNA is essential for life. Despite the proofreading capability of several polymerases, intrinsic polymerase fidelity is in general much higher than what base-pairing energies can provide. Although researchers have investigated this long-standing question with kinetics, structural determination, and computational simulations, the structural factors that dictate polymerase fidelity are not fully resolved. Time-resolved crystallography has elucidated correct nucleotide incorporation and established a three-metal-ion-dependent catalytic mechanism for polymerases. Using X-ray time-resolved crystallography, we visualize the complete DNA misincorporation process catalyzed by DNA polymerase η. The resulting molecular snapshots suggest primer 3´-OH alignment mediated by A-site metal ion binding is the key step in substrate discrimination. Moreover, we observe that C-site metal ion binding preceded the nucleotidyl transfer reaction and demonstrate that the C-site metal ion is strictly required for misincorporation. Our results highlight the essential but separate roles of the three metal ions in DNA synthesis. | |
| dc.identifier.citation | Chang, Caleb, Lee Luo, Christie and Gao, Yang. "In crystallo observation of three metal ion promoted DNA polymerase misincorporation." <i>Nature Communications,</i> 13, (2022) Springer Nature: https://doi.org/10.1038/s41467-022-30005-3. | |
| dc.identifier.digital | s41467-022-30005-3 | |
| dc.identifier.doi | https://doi.org/10.1038/s41467-022-30005-3 | |
| dc.identifier.uri | https://hdl.handle.net/1911/112421 | |
| dc.language.iso | eng | |
| dc.publisher | Springer Nature | |
| dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. | |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.title | In crystallo observation of three metal ion promoted DNA polymerase misincorporation | |
| dc.type | Journal article | |
| dc.type.dcmi | Text | |
| dc.type.publication | publisher version |
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