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G-quadruplex nucleic acids and human disease.

Authors
  • Wu, Yuliang1
  • Brosh, Robert M Jr
  • 1 Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA.
Type
Published Article
Journal
FEBS Journal
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2010
Volume
277
Issue
17
Pages
3470–3488
Identifiers
DOI: 10.1111/j.1742-4658.2010.07760.x
PMID: 20670277
Source
Medline
License
Unknown

Abstract

Alternate DNA structures that deviate from B-form double-stranded DNA such as G-quadruplex (G4) DNA can be formed by sequences that are widely distributed throughout the human genome. G-quadruplex secondary structures, formed by the stacking of planar quartets composed of four guanines that interact by Hoogsteen hydrogen bonding, can affect cellular DNA replication and transcription, and influence genomic stability. The unique metabolism of G-rich chromosomal regions that potentially form quadruplexes may influence a number of biological processes including immunoglobulin gene rearrangements, promoter activation and telomere maintenance. A number of human diseases are characterized by telomere defects, and it is proposed that G-quadruplex structures which form at telomere ends play an important role in telomere stability. Evidence from cellular studies and model organisms suggests that diseases with known defects in G4 DNA helicases are likely to be perturbed in telomere maintenance and cellular DNA replication. In this minireview, we discuss the connections of G-quadruplex nucleic acids to human genetic diseases and cancer based on the recent literature.

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