Stabilization of a G-quadruplex from unfolding by replication protein A using potassium and the porphyrin TMPyP4

Aishwarya Prakash, Fabien Kieken, Luis A. Marky, Gloria E O Borgstahl

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Replication protein A (RPA) plays an essential role in DNA replication by binding and unfolding non-canonical single-stranded DNA (ssDNA) structures. Of the six RPA ssDNA binding domains (labeled A-F), RPA-CDE selectively binds a G-quadruplex forming sequence (5′ -TAGGGGAAGGGTTGGAGTGGGTT- 3′ called Gq23). In K+, Gq23 forms a mixed parallel/antiparallel conformation, and in Na+ Gq23 has a less stable (T M lowered by ∼ 20 ° C), antiparallel conformation. Gq23 is intramolecular and 1D NMR confirms a stable G-quadruplex structure in K+. Full-length RPA and RPA-CDE-core can bind and unfold the Na+ form of Gq23 very efficiently, but complete unfolding is not observed with the K+ form. Studies with G-quadruplex ligands, indicate that TMPyP4 has a thermal stabilization effect on Gq23 in K+, and inhibits complete unfolding by RPA and RPA-CDE-core. Overall these data indicate that G-quadruplexes present a unique problem for RPA to unfold and ligands, such as TMPyP4, could possibly hinder DNA replication by blocking unfolding by RPA.

Original languageEnglish (US)
Article number529828
JournalJournal of Nucleic Acids
Volume2011
DOIs
StatePublished - 2011
Externally publishedYes

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Replication Protein A
G-Quadruplexes
Porphyrins
Potassium
Stabilization
Single-Stranded DNA
DNA Replication
Conformations
Ligands
tetra(4-N-methylpyridyl)porphine
DNA
Hot Temperature
Nuclear magnetic resonance

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Stabilization of a G-quadruplex from unfolding by replication protein A using potassium and the porphyrin TMPyP4. / Prakash, Aishwarya; Kieken, Fabien; Marky, Luis A.; Borgstahl, Gloria E O.

In: Journal of Nucleic Acids, Vol. 2011, 529828, 2011.

Research output: Contribution to journalArticle

Prakash, Aishwarya ; Kieken, Fabien ; Marky, Luis A. ; Borgstahl, Gloria E O. / Stabilization of a G-quadruplex from unfolding by replication protein A using potassium and the porphyrin TMPyP4. In: Journal of Nucleic Acids. 2011 ; Vol. 2011.
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