Slipped strand mispairing

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]

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.[2]

Slipped strand mispairing has also been shown to function as a phase variation mechanism in certain bacteria.[3]

Self-acceleration

SSM events can result in either insertions or deletions. Insertions are thought to be self-accelerating: as repeats grow longer, the probability of subsequent mispairing events increases. Insertions can expand simple tandem repeats by one or more units. In long repeats, expansions may involve two or more units. For example, insertion of a single repeat unit in GAGAGA expands the sequence to GAGAGAGA, while insertion of two repeat units in [GA]6 would produce [GA]8. Genomic regions with a high proportion of repeated DNA sequences (tandem repeats, microsatellites) are prone to strand slippage during DNA replication and DNA repair.

Trinucleotide repeat expansion is a cause of a number of human diseases including fragile X syndrome, Huntington’s disease, several spinocerebellar ataxias, myotonic dystrophy and Friedrich ataxia.[2]

Evolution of diverse adjacent repeats

The combination of SSM events with point mutation is thought to account for the evolution of more complex repeat units. Mutations followed by expansion would result in the formation of new types of adjacent short tandem repeat units. For example, a transversion could change the simple two- base repeat [GA]10 to [GA]4GATA[GA]2. This could then be expanded to[GA]4[GATA]3[GA]2 by two subsequent SSM events. Simple repetitive DNA sequences containing a variety of adjacent short tandem repeats are commonly observed in non-protein coding regions of eukaryotic genomes.

References

  1. ↑ Levinson, G. & Gutman, G. A. (1987). "Slipped-Strand Mispairing: A Major Mechanism for DNA Sequence Evolution". Mol. Biol. Evol. 4 (3): 203–221. PMID 3328815.
  2. 1 2 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.
  3. ↑ Torres-Cruz, Joshua and van der Woude, Marjan W. (2003). "Slipped-Strand Mispairing Can Function as a Phase Variation Mechanism in Escherichia coli". Journal of Bacteriology. 185 (23): 6990–6994. doi:10.1128/JB.185.23.6990-6994.2003. PMC 262711. PMID 14617664.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.