5GWL

Structure of two CCTG repeats

Summary for 5GWL

• Entry DOI: 10.2210/pdb5gwl/pdb
• Related: 5GWQ
• NMR Information: BMRB: 36020
• Descriptor: DNA (5'-D(*CP*CP*TP*GP*CP*CP*TP*G)-3'), SODIUM ION (2 entities in total)
• Functional Keywords: minidumbbell, type ii loop, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 2539.50

Authors

Guo, P.,Lam, S.L. (deposition date: 2016-09-12, release date: 2016-10-12, Last modification date: 2024-05-01)

Primary citation

Guo, P.,Lam, S.L.
Minidumbbell: A New Form of Native DNA Structure
J.Am.Chem.Soc., 138:12534-12540, 2016

PubMed Abstract: The non-B DNA structures formed by short tandem repeats on the nascent strand during DNA replication have been proposed to be the structural intermediates that lead to repeat expansion mutations. Tetranucleotide TTTA and CCTG repeat expansions have been known to cause reduction in biofilm formation in Staphylococcus aureus and myotonic dystrophy type 2 in human, respectively. In this study, we report the first three-dimensional minidumbbell (MDB) structure formed by natural DNA sequences containing two TTTA or CCTG repeats. The formation of MDB provides possible pathways for strand slippage to occur, which ultimately leads to repair escape and thus expansion mutations. Our result here shows that MDB is a highly compact structure composed of two type II loops. In addition to the typical stabilizing interactions in type II loops, MDB shows extensive stabilizing forces between the two loops, including two distinctive modes of interactions between the minor groove residues. The formation of MDB enriches the structural diversity of natural DNA sequences, reveals the importance of loop-loop interactions in unusual DNA structures, and provides insights into novel mechanistic pathways of DNA repeat expansion mutations.

PubMed: 27589409
DOI: 10.1021/jacs.6b06897

Experimental method

SOLUTION NMR