The Role of Cytosine Methylation in Regulating the Topology and Liquid-liquid Phase Separation of DNA G-quadruplexes

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2025 Feb 12

PMID 39935503

Authors

Mitsuki Tsuruta

Sumit Shil

Shinya Taniguchi

Keiko Kawauchi

Daisuke Miyoshi

Affiliations

Soon will be listed here.

Abstract

Aberrant expansion of GGGGCC DNA repeats that form G-quadruplexes (G4) is the main cause of amyotrophic lateral sclerosis (ALS). Expanded GGGGCC repeats induce liquid-liquid phase separation (LLPS) through their interaction with cellular proteins. Furthermore, GGGGCC expansion induces cytosine methylation (mC). Previous studies have shown that even slight chemical modifications of RNAs and proteins can drastically affect their LLPS ability, yet the relationship between LLPS and epigenetic DNA modifications like mC remains unexplored. As a model system, we investigated the effects of mC on LLPS induced by GGGGCC repeat DNAs and show for the first time that mC suppresses LLPS by altering the topology of G4 from being parallel to antiparallel.

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