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Related Concept Videos

Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

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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...
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In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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Interactions of small molecules with DNA junctions.

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Alternative DNA structures, beyond the canonical double helix, offer diverse forms like base triplets and quartets. These structures, including three- and four-way junctions, are emerging as key therapeutic targets for genetic diseases.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Chemical Biology
  • Genetics

Background:

  • DNA typically forms a double helix (B-DNA) through base pairing (A=T, G≡C).
  • Nucleobase properties allow for alternative DNA structures beyond B-DNA, including triplets and quartets.
  • Approximately 20 different DNA structures exist, but only a few are biologically significant and therapeutically relevant.

Approach:

  • This review summarizes the characteristics of alternative DNA structures, including their formation and biological roles.
  • It focuses on specific structures, such as three- and four-way DNA junctions, as valuable therapeutic targets.
  • The review discusses molecular tools (ligands) developed to target these alternative DNA structures.

Key Points:

  • Alternative DNA structures exhibit diverse topologies beyond the canonical B-DNA form.
  • Three- and four-way DNA junctions are highlighted as critical targets for chemical biology interventions.
  • Development of specific ligands enables precise targeting of these non-canonical DNA structures.

Conclusions:

  • Alternative DNA structures represent a rich area for exploring novel therapeutic strategies.
  • Targeting these structures offers innovative approaches to combat genetic diseases.
  • Chemical biology provides the tools to exploit alternative DNA structures for therapeutic benefit.