Global InformationSlipped strand mispairing information
Slipped strand mispairing (SSM, also known as replication slippage) is a mutation process which occurs during DNA replication. It involves denaturation and displacement of the DNA strands, resulting in mispairing of the complementary bases. Slipped strand mispairing is one explanation for the origin and evolution of repetitive DNA sequences.[1]
It is a form of mutation that leads to either a trinucleotide or dinucleotide expansion, or sometimes contraction, during DNA replication.[2] A slippage event normally occurs when a sequence of repetitive nucleotides (tandem repeats) are found at the site of replication. Tandem repeats are unstable regions of the genome where frequent insertions and deletions of nucleotides can take place, resulting in genome rearrangements.[3] DNA polymerase, the main enzyme to catalyze the polymerization of free deoxyribonucleotides into a newly forming DNA strand, plays a significant role in the occurrence of this mutation. When DNA polymerase encounters a direct repeat, it can undergo a replication slippage.[4]
Strand slippage may also occur during the DNA synthesis step of DNA repair processes. Within DNA trinucleotide repeat sequences, the repair of DNA damage by the processes of homologous recombination, non-homologous end joining, DNA mismatch repair or base excision repair may involve strand slippage mispairing leading to trinucleotide repeat expansion when the repair is completed.[5]
Slipped strand mispairing has also been shown to function as a phase variation mechanism in certain bacteria.[6]
- ^ Levinson G, Gutman GA (May 1987). "Slipped-strand mispairing: a major mechanism for DNA sequence evolution". Mol. Biol. Evol. 4 (3): 203–21. doi:10.1093/oxfordjournals.molbev.a040442. PMID 3328815.
- ^ Hartl L.D and Ruvolo M, 2012, Genetic Analysis of Genes and Genomes, Jones & Bartlett Learning, Burlington, pg. 529
- ^ Lovett, S.T.; Drapkin, P.T.; Sutera, V.A. Jr.; Gluckman-Peskind, T.J. (1993). "A sister-strand exchange mechanism for recA-independent deletion of repeated DNA sequences in Escherichia coli". Genetics. 135 (3): 631–642. doi:10.1093/genetics/135.3.631. PMC 1205708. PMID 8293969.
- ^ Viguera, E; Canceill, D; Ehrlich, SD. (2001). "Replication slippage involves DNA polymerase pausing and dissociation". The EMBO Journal. 20 (10): 2587–2595. doi:10.1093/emboj/20.10.2587. PMC 125466. PMID 11350948.
- ^ Usdin K, House NC, Freudenreich CH (2015). "Repeat instability during DNA repair: Insights from model systems". Crit. Rev. Biochem. Mol. Biol. 50 (2): 142–67. doi:10.3109/10409238.2014.999192. PMC 4454471. PMID 25608779.
- ^ Torres-Cruz J, van der Woude MW (December 2003). "Slipped-strand mispairing can function as a phase variation mechanism in Escherichia coli". J. Bacteriol. 185 (23): 6990–4. doi:10.1128/jb.185.23.6990-6994.2003. PMC 262711. PMID 14617664.