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Inhibition of DNA synthesis facilitates expansion of low‐complexity repeats
Author(s) -
Kuzminov Andrei
Publication year - 2013
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201200128
Subject(s) - dna replication , biology , minisatellite , dna , semiconservative replication , genetics , trinucleotide repeat expansion , repeated sequence , primer (cosmetics) , dna clamp , dna synthesis , dna polymerase , microbiology and biotechnology , eukaryotic dna replication , computational biology , chemistry , microsatellite , polymerase chain reaction , gene , genome , reverse transcriptase , allele , organic chemistry
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.