Insights & Perspectives
Inhibition of DNA synthesis facilitates expansion of low-complexity repeats
Is strand slippage stimulated by transient local depletion of specific dNTPs?
Version of Record online: 15 JAN 2013
Copyright © 2013 WILEY Periodicals, Inc.
Volume 35, Issue 4, pages 306–313, April 2013
How to Cite
Kuzminov, A. (2013), Inhibition of DNA synthesis facilitates expansion of low-complexity repeats. Bioessays, 35: 306–313. doi: 10.1002/bies.201200128
- Issue online: 14 MAR 2013
- Version of Record online: 15 JAN 2013
- DNA synthesis inhibition;
- dNTP pools;
- repeat instability;
- strand slippage;
- trinucleotide repeats
Simple DNA repeats (trinucleotide repeats, micro- and minisatellites) are prone to expansion/contraction via formation of secondary structures during DNA synthesis. Such structures both inhibit replication forks and create opportunities for template-primer slippage, making these repeats unstable. Certain aspects of simple repeat instability, however, suggest additional mechanisms of replication inhibition dependent on the primary DNA sequence, rather than on secondary structure formation. I argue that expanded simple repeats, due to their lower DNA complexity, should transiently inhibit DNA synthesis by locally depleting specific DNA precursors. Such transient inhibition would promote formation of secondary structures and would stabilize these structures, facilitating strand slippage. Thus, replication problems at simple repeats could be explained by potentiated toxicity, where the secondary structure-driven repeat instability is enhanced by DNA polymerase stalling at the low complexity template DNA.
This minireview is dedicated to the FASEB-2012 meeting “Dynamic DNA Structures in Biology”, organized by Nancy Maizels and Sergei Mirkin.