G-Quadruplexes: A Role In The Mitochondrial Genome Stability

Document Type

Poster Session

Publication Date

8-1-2016

Published In

Biochimica Et Biophysica Acta (BBA) - Bioenergetics

Abstract

Single-stranded DNA or RNA regions rich in guanine (G) sequences can adopt non-canonical G-quadruplexes (G4) structures through the formation of Hoogsteen hydrogen bonds. Several studies report the existence of G4 structure formation both in vitro and in vivo, and have established their biological importance in nuclear DNA replication, transcriptional regulation and genome stability [1,2]. Genomic events, such as replication, lead to single-strand DNA formation and increase the probability of G4 formation, which could contribute to genome instability both in nuclear and mitochondrial DNA (mtDNA). The mitochondrial genome is present in thousands of copies per cell as a double-stranded circular molecule of 16 kb, encoding 13 proteins essential to oxidative phosphorylation (OXPHOS) and the RNAs necessary for their translation. Our recent in vitro study established that mtDNA has the potential to form G4 structures [3]. The same study demonstrated a tight correlation between G4 motifs and mtDNA deletion breakpoints, supporting a role for the G-quadruplexes in genome instability. To better understand the biological function of G-quadruplexes in mitochondria, we screened G4 stabilizing ligands for effects on mtDNA abundance. Here we report the activity a specific mitochondrial GQ ligand on mtDNA stability, gene expression and mitochondrial respiration.

Conference

European Bioenergetics Conference

Conference Dates

July 2-7, 2016

Conference Location

Riva Del Garda, Italy

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