Fluorescent molecular rotors detect O6-methylguanine dynamics and repair in duplex DNA

文献情報

出版日 2023-12-19

DOI 10.1039/D3CC04782B

インパクトファクター 6.222

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要旨

Alkylation at the O6 position of guanine is a common and highly mutagenic form of DNA damage. Direct repair of O6-alkylguanines by the “suicide” enzyme O6-methylguanine DNA methyltransferase (MGMT, AGT, AGAT) maintains genome stability and inhibits carcinogenesis. In this study, a fluorescent analogue of thymidine containing trans-stilbene (tsT) is quenched by O6-methylguanine residues in the opposite strand of DNA by molecular dynamics that propagate through the duplex with as much as ∼9 Å of separation. Increased fluorescence of tsT or the cytosine analogue tsC resulting from MGMT-mediated DNA repair were distinguishable from non-covalent DNA–protein binding following protease digest. To our knowledge, this is the first study utilizing molecular rotor base analogues to detect DNA damage and repair activities in duplex DNA.

掲載誌

Chemical Communications

CiteScore: 8.6

自己引用率: 4.7%

年間論文数: 2458

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