Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis
High fidelity replicative DNA polymerases are unable to synthesize past DNA adducts that result from diverse chemicals, reactive oxygen species or UV light. To bypass these replication blocks, cells utilize specialized translesion DNA polymerases that are intrinsically error prone and associated wit...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32177 |
| _version_ | 1828380072817459200 |
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| author | Gengjing Zhao Emma S Gleave Meindert Hugo Lamers |
| author_facet | Gengjing Zhao Emma S Gleave Meindert Hugo Lamers |
| author_sort | Gengjing Zhao |
| collection | DOAJ |
| description | High fidelity replicative DNA polymerases are unable to synthesize past DNA adducts that result from diverse chemicals, reactive oxygen species or UV light. To bypass these replication blocks, cells utilize specialized translesion DNA polymerases that are intrinsically error prone and associated with mutagenesis, drug resistance, and cancer. How untimely access of translesion polymerases to DNA is prevented is poorly understood. Here we use co-localization single-molecule spectroscopy (CoSMoS) to follow the exchange of the E. coli replicative DNA polymerase Pol IIIcore with the translesion polymerases Pol II and Pol IV. We find that in contrast to the toolbelt model, the replicative and translesion polymerases do not form a stable complex on one clamp but alternate their binding. Furthermore, while the loading of clamp and Pol IIIcore is highly organized, the exchange with the translesion polymerases is stochastic and is not determined by lesion-recognition but instead a concentration-dependent competition between the polymerases. |
| first_indexed | 2024-12-10T03:51:59Z |
| format | Article |
| id | doaj.art-e8e28c7d52dc4690acbae68874c60f42 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:51:59Z |
| publishDate | 2017-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e8e28c7d52dc4690acbae68874c60f422022-12-22T02:03:15ZengeLife Sciences Publications LtdeLife2050-084X2017-12-01610.7554/eLife.32177Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesisGengjing Zhao0Emma S Gleave1Meindert Hugo Lamers2https://orcid.org/0000-0002-4205-1338MRC laboratory of Molecular Biology, Cambridge, United KingdomMRC laboratory of Molecular Biology, Cambridge, United KingdomMRC laboratory of Molecular Biology, Cambridge, United KingdomHigh fidelity replicative DNA polymerases are unable to synthesize past DNA adducts that result from diverse chemicals, reactive oxygen species or UV light. To bypass these replication blocks, cells utilize specialized translesion DNA polymerases that are intrinsically error prone and associated with mutagenesis, drug resistance, and cancer. How untimely access of translesion polymerases to DNA is prevented is poorly understood. Here we use co-localization single-molecule spectroscopy (CoSMoS) to follow the exchange of the E. coli replicative DNA polymerase Pol IIIcore with the translesion polymerases Pol II and Pol IV. We find that in contrast to the toolbelt model, the replicative and translesion polymerases do not form a stable complex on one clamp but alternate their binding. Furthermore, while the loading of clamp and Pol IIIcore is highly organized, the exchange with the translesion polymerases is stochastic and is not determined by lesion-recognition but instead a concentration-dependent competition between the polymerases.https://elifesciences.org/articles/32177single-moleculeDNA replicationtranslesion DNA synthesisCoSMoS |
| spellingShingle | Gengjing Zhao Emma S Gleave Meindert Hugo Lamers Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis eLife single-molecule DNA replication translesion DNA synthesis CoSMoS |
| title | Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis |
| title_full | Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis |
| title_fullStr | Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis |
| title_full_unstemmed | Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis |
| title_short | Single-molecule studies contrast ordered DNA replication with stochastic translesion synthesis |
| title_sort | single molecule studies contrast ordered dna replication with stochastic translesion synthesis |
| topic | single-molecule DNA replication translesion DNA synthesis CoSMoS |
| url | https://elifesciences.org/articles/32177 |
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