Double-Stranded G4-Stack:
A Possible Structural Motif in Eucaryotic Chromosomes

Ko-Hsin Chin & Shan-Ho Chou*

Institute of Biochemistry

National Chung-Hsing University, Taichung, 40227, Taiwan

 

DNA sequences containing homopurine d(GGGA) tract are abundant at genomic locations performing specialized functions (i.e. centromeres, telomeres, and recombination hot spots). They are capable of forming fold-back structures at physiological condition. In this manuscript, we describe a “double-intercalation” G-4 stack structure in the homopurine d(GGGA) tract embedded in the stem of several DNA hairpins using high resolution nuclear magnetic resonance (NMR) and molecular dynamics (MD) techniques. Similar to the zipper-like d(GGA)2 motif observed in the human centromeric (TGGAA)n sequence, the central two pairs of guanosine exhibit no H-bonding but intercalate on top of each other to form a consecutive G-4 stack bracketed by sheared G·A base pairs. The G-4 stack containing hairpin turned out to be stable with UV melting temperature at 55 °C even though only four out of nine potential base pairs are engaged in canonical G·C and A·T H-bonding. The characteristically very thin minor groove and very broad major groove and the very different H-bonding donor and acceptor profile in the major groove may play important roles in the organization of eucaryotic chromosomes.