Premium
“Repaired and Activated” DNAzyme Enables the Monitoring of DNA Alkylation Repair in Live Cells
Author(s) -
Wang Xiangnan,
Yi Xin,
Huang Zhimei,
He Jianjun,
Wu Zhenkun,
Chu Xia,
Jiang JianHui
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202106557
Subject(s) - dna repair , deoxyribozyme , dna , lesion , computational biology , dna damage , dna damage repair , proliferating cell nuclear antigen , cancer research , chemistry , biology , medicine , biochemistry , pathology
Abstract Direct measurement of DNA repair is critical for the annotation of their clinical relevance and the discovery of drugs for cancer therapy. Here we reported a “repaired and activated” DNAzyme (RADzyme) by incorporating a single methyl lesion (O 6 MeG, 3MeC, or 1MeA) at designated positions through systematic screening. We found that the catalytic activity of the RADzyme was remarkably suppressed and could be restored via enzyme‐mediated DNA repair. Benefit from these findings, a fluorogenic RADzyme sensor was developed for the monitoring of MGMT‐mediated repair of O 6 MeG lesion. Importantly, the sensor allowed the evaluation of MGMT repair activity in different cells and under drugs treatment. Furthermore, another RADzyme sensor was engineered for the monitoring of ALKBH2‐mediated repair of 3MeC lesion. This strategy provides a simple and versatile tool for the study of the basic biology of DNA repair, clinical diagnosis and therapeutic assessment.