Cytosine Quadruplexes in Duplex DNA may be Non-transient and have Epigenetic Relevance

Abstract

Guanine quadruplexes folding in single-strand DNA have been extensively studied for some time. But far less attention has been paid to systems arising in duplex DNA. Furthermore, the literature shows an apparent absence of quadruplex systems generated exclusively by other nucleic acid bases. This study investigates biplanar and triplanar complexes folding in double-strand DNA when derived from cytosine (C4s). The role of various co-ordinating cations was also investigated. Molecular dynamics simulations determined triplanar models as relatively fragile systems, but all biplanar systems were found to be stable into biologically relevant times. Cationic co-ordination in biplanar systems appears to be much less contributive to stability than in triplanar equivalents. Uniquely biplanar or triplanar C4s have ostensibly not been previously described. It is suggested here that these structures folding in the human genome may have physiological relevance even if relatively short-lived. A non-transient folding / unfolding cycle might persist and influence epigenetic processes.