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Nanopore Sequencing Accurately Identifies the Mutagenic DNA Lesion O; 6; -Carboxymethyl Guanine and Reveals Its Behavior in Replication

Wang, Yu and Patil, Kiran M. and Yan, Shuanghong and Zhang, Panke and Guo, Weiming and Wang, Yuqin and Chen, Hong-Yuan and Gillingham, Dennis and Huang, Shuo. (2019) Nanopore Sequencing Accurately Identifies the Mutagenic DNA Lesion O; 6; -Carboxymethyl Guanine and Reveals Its Behavior in Replication. Angewandte Chemie International Edition, 58 (25). pp. 8432-8436.

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Official URL: https://edoc.unibas.ch/74577/

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Abstract

O; 6; -carboxymethylguanine (O; 6; -CMG) is a highly mutagenic alkylation product of DNA, triggering transition mutations relevant to gastrointestinal cancer. However, precise localization of a single O; 6; -CMG with conventional sequencing platforms is challenging. Here nanopore sequencing (NPS), which directly senses single DNA bases according to their physiochemical properties, was employed to detect O; 6; -CMG. A unique O; 6; -CMG signal was observed during NPS and a single-event call accuracy of >95 % was achieved. Moreover, O; 6; -CMG was found to be a replication obstacle for Phi29 DNA polymerase (Phi29 DNAP), suggesting this lesion could cause DNA sequencing biases in next generation sequencing (NGS) approaches.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Organische Chemie (Gillingham)
UniBasel Contributors:Gillingham, Dennis
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:1433-7851
e-ISSN:1521-3773
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:14 May 2020 09:39
Deposited On:21 Jan 2020 12:17

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