Rationally designed DNA therapeutics can modulate human TH expression by controlling specific GQ formation in its promoter

Beals, Nathan; Farhath, Mohamed M.; Kharel, Prakash; Croos, Brintha; Mahendran, Thulasi; Johnson, John D.; Basu, Soumitra

doi:10.1016/j.ymthe.2021.05.013

Cited by 5 publications

(1 citation statement)

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“…Intensive studies of DNA and RNA G-quadruplexes (GQs) in recent decades have revealed their doubtless role in transcriptional control [1,2], telomere function, and epigenetic events [3]. The functionality of many cellular proteins is implemented through their binding with GQ sites, as demonstrated for a number of transcription factors [4], the RTEL1 protein [5], some DNA methyltransferases [3], and nucleolin [6].…”

Section: Introductionmentioning

confidence: 99%

Recognition Interface of the Thrombin Binding Aptamer Requires Antiparallel Topology of the Quadruplex Core

et al. 2021

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Recent advances in G-quadruplex (GQ) studies have provided evidence for their important role in key biological processes (replication, transcription, genome stability, and epigenetics). These findings imply highly specific interactions between GQ structures and cellular proteins. The details of the interaction between GQs and cellular proteins remain unknown. It is now accepted that GQ loop elements play a major role in protein recognition. It remains unclear whether and to what extent the GQ core contributes to maintaining the recognition interface. In the current paper, we used the thrombin binding aptamer as a model to study the effect of modification in the quadruplex core on the ability of aptamer to interact with thrombin. We used alpha-2′-deoxyguanosine and 8-bromo-2′-deoxyguanosine to reconfigure the core or to affect syn–anti preferences of selected dG-residues. Our data suggest that core guanines not only support a particular type of GQ architecture, but also set structural parameters that make GQ protein recognition sensitive to quadruplex topology.

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