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Related Concept Videos

Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
Proofreading01:31

Proofreading

Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore,  it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase Enzyme
Proofreading01:43

Proofreading

Synthesis of new DNA molecules starts when DNA polymerase links nucleotides together in a sequence that is complementary to the template DNA strand. DNA polymerase has a higher affinity for the correct base to ensure fidelity in DNA replication. The DNA polymerase furthermore proofreads during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.Errors during Replication Are Corrected by the DNA Polymerase EnzymeGenomic DNA is synthesized in...
DNA Base Pairing02:27

DNA Base Pairing

Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,

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Related Experiment Video

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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
09:04

Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids

Published on: September 21, 2017

Loop and backbone modifications of peptide nucleic acid improve g-quadruplex binding selectivity.

Sabrina Lusvarghi1, Connor T Murphy, Subhadeep Roy

  • 1Departments of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.

Journal of the American Chemical Society
|December 2, 2009
PubMed
Summary

Researchers modified guanine-rich peptide nucleic acid (PNA) oligomers to enhance selectivity for G-quadruplex formation over duplexes. Backbone modifications improved PNA binding to target DNA and RNA, advancing gene regulation and anticancer agent development.

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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • Guanine (G)-rich quadruplex structures are key targets for gene expression control and anticancer drug design.
  • Peptide nucleic acid (PNA) oligomers can bind DNA/RNA to form G-quadruplexes or duplexes, but selectivity is a challenge.

Purpose of the Study:

  • To develop G-rich PNA oligomers with improved selectivity for G-quadruplex formation over duplex formation.
  • To investigate backbone modifications that enhance PNA binding specificity.

Main Methods:

  • Incorporation of abasic sites and chiral modifications into the PNA backbone.
  • Evaluation of PNA selectivity using UV-melting and surface plasmon resonance (SPR) measurements.

Main Results:

  • Backbone modifications significantly improved PNA selectivity for quadruplex formation.
  • Selectivity enhancement resulted from decreased affinity for complementary sequences.
  • High affinity for homologous DNA to form PNA-DNA heteroquadruplexes was maintained.

Conclusions:

  • Modified G-rich PNAs demonstrate enhanced selectivity for G-quadruplex formation.
  • These findings represent a significant advancement in developing PNAs for gene regulation via G-quadruplexes.
  • The improved PNA design holds promise for novel anticancer therapeutic strategies.