The hidden side of unstable DNA repeats: Mutagenesis at a distance.

Abstract

Structure-prone DNA repeats are common components of genomic DNA in all kingdoms of life. In humans, these repeats are linked to genomic instabilities that result in various hereditary disorders, including many cancers. It has long been known that DNA repeats are not only highly polymorphic in length but can also cause chromosomal fragility and stimulate gross chromosomal rearrangements, i.e., deletions, duplications, inversions, translocations and more complex shuffles. More recently, it has become clear that inherently unstable DNA repeats dramatically elevate mutation rates in surrounding DNA segments and that these mutations can occur up to ten kilobases away from the repetitive tract, a phenomenon we call repeat-induced mutagenesis (RIM). This review describes experimental data that led to the discovery and characterization of RIM and discusses the molecular mechanisms that could account for this phenomenon.

• Authors: Kartik A Shah, Sergei M Mirkin
• Journal: DNA repair (DNA Repair (Amst)) Vol. 32 Pg. 106-112 (Aug 2015) ISSN: 1568-7856 [Electronic] Netherlands
• PMID: 25956860 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Iron-Binding Proteins
• frataxin
• DNA

Topics

• Chromosome Aberrations
• Chromosome Fragility
• Chromosomes, Human, Pair 9
• DNA (chemistry, metabolism)
• DNA Damage
• DNA Repair
• Friedreich Ataxia (genetics, metabolism, pathology)
• Humans
• Iron-Binding Proteins (genetics, metabolism)
• Mutagenesis
• Mutation Rate
• Trinucleotide Repeat Expansion