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© Research
Publication : Current genetics

Trinucleotide repeat instability during double-strand break repair: from mechanisms to gene therapy.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Current genetics - 01 Feb 2019

Mosbach V, Poggi L, Richard GF,

Link to Pubmed [PMID] – 29974202

Link to DOI – 10.1007/s00294-018-0865-1

Curr Genet 2019 Feb; 65(1): 17-28

Trinucleotide repeats are a particular class of microsatellites whose large expansions are responsible for at least two dozen human neurological and developmental disorders. Slippage of the two complementary DNA strands during replication, homologous recombination or DNA repair is generally accepted as a mechanism leading to repeat length changes, creating expansions and contractions of the repeat tract. The present review focuses on recent developments on double-strand break repair involving trinucleotide repeat tracts. Experimental evidences in model organisms show that gene conversion and break-induced replication may lead to large repeat tract expansions, while frequent contractions occur either by single-strand annealing between repeat ends or by gene conversion, triggering near-complete contraction of the repeat tract. In the second part of this review, different therapeutic approaches using highly specific single- or double-strand endonucleases targeted to trinucleotide repeat loci are compared. Relative efficacies and specificities of these nucleases will be discussed, as well as their potential strengths and weaknesses for possible future gene therapy of these dramatic disorders.

https://pubmed.ncbi.nlm.nih.gov/29974202