Slippedstrand

Slippedstrand is a term used to describe a DNA replication error characterized by misalignment between the template and nascent strands in regions of repetitive sequence, leading to insertions or deletions in the copied DNA. In practice it corresponds to the well-studied phenomenon of slipped-strand mispairing (SSM) during DNA synthesis. The mechanism involves transient loop formation in the newly synthesized strand or in the template strand when the polymerase encounters short tandem repeats. If the loop occurs on the template strand, the polymerase reads through the loop, creating a deletion in the copied strand; if the loop is on the daughter strand, an insertion results. The repetition unit length and number influence the likelihood and the size of the indel, commonly generating changes in microsatellites or trinucleotide repeats.

Impact: Slippedstrand contributes to genetic variation within populations and to mutation load. In coding regions, it can cause frameshift mutations; in noncoding regions, it alters repeat length and can affect gene regulation. Repeats prone to slipping include dinucleotide and trinucleotide repeats. The process is mitigated by proofreading and the mismatch repair pathway, which corrects mispaired bases and small loops.

Detection and study: Researchers detect slippage events by sizing repetitive regions via PCR and capillary electrophoresis, or by sequencing genomes across organisms. In disease genetics, length changes in repeats are linked to instability syndromes and certain neurodegenerative diseases.

See also: microsatellite instability, replication slippage, mismatch repair, repeat expansion, hairpin structures.