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Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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Nucleosome Remodeling02:54

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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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DNA Topoisomerases02:02

DNA Topoisomerases

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Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
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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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RNA Structure01:19

RNA Structure

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The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
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Loop flexibility in human telomeric quadruplex small-molecule complexes.

Gavin W Collie1, Nancy H Campbell1, Stephen Neidle2

  • 1UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.

Nucleic Acids Research
|May 6, 2015
PubMed
Summary
This summary is machine-generated.

Small molecules stabilize telomeric quadruplexes, inhibiting cancer cell telomerase. Crystal structures reveal loop variations, aiding rational drug design for cancer therapeutics.

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Medicinal Chemistry

Background:

  • Quadruplex nucleic acids form at eukaryotic chromosome ends.
  • Telomerase maintains telomeres, crucial for cancer cell proliferation.
  • Small molecules can stabilize quadruplexes to inhibit telomerase.

Purpose of the Study:

  • To analyze the structural characteristics of small molecule-quadruplex complexes.
  • To explore variations in TTA and UUA loop conformations.
  • To provide insights for rational drug design targeting telomerase.

Main Methods:

  • X-ray crystallography to determine complex structures.
  • Structural analysis of human telomeric DNA and RNA quadruplexes.
  • Classification and distribution analysis of loop conformations.

Main Results:

  • Detailed structural features of small molecule-quadruplex complexes were surveyed.
  • Variations in TTA and UUA loop conformations were classified into discrete types.
  • One specific loop conformation class was identified as most prevalent.

Conclusions:

  • Structural insights into quadruplex-small molecule interactions are crucial.
  • Understanding loop conformations aids in designing selective telomerase inhibitors.
  • This research supports the development of novel anti-cancer drugs.