The transcription-coupled repair protein ERCC6/CSB also protects against repeat expansion in a mouse model of the fragile X premutation.
The fragile X-related disorders (FXDs) are members of the group of diseases known as the repeat expansion diseases. The FXDs result from expansion of an unstable CGG/CCG repeat tract in the 5' UTR of the FMR1 gene. Contractions are also seen, albeit at lower frequency. We have previously shown that ERCC6/CSB plays an auxiliary role in promoting germ line and somatic expansions in a mouse model of the FXDs. However, work in model systems of other repeat expansion diseases has suggested that CSB may protect against expansions by promoting contractions. Since FXD mice normally have such a high expansion frequency, it is possible that such a protective effect would have been masked. We thus examined the effect of the loss of CSB in an Msh2(+/-) background where the germ line expansion frequency is reduced and in an Msh2(-/-) background where expansions do not occur, but contractions do. Our data show that in addition to promoting repeat expansion, CSB does in fact protect the genome from germ line expansions in the FXD mouse model. However, it likely does so not by promoting contractions but by promoting an error-free process that preserves the parental allele.
Section on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Xiao-Nan
XN
Zhao
Karen
K
Usdin
D000818:Animals; D045643:DNA Repair Enzymes / Q000172:deficiency / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D017353:Gene Deletion; D042822:Genomic Instability; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051718:MutS Homolog 2 Protein / Q000172:deficiency; D000075223:Poly-ADP-Ribose Binding Proteins; D014158:Transcription, Genetic; D019680:Trinucleotide Repeat Expansion
D000075223:Poly-ADP-Ribose Binding Proteins; D051718:MutS Homolog 2 Protein; C513075:Ercc6 protein, mouse; D045643:DNA Repair Enzymes
CSB; ERCC6; FMR1; FX-associated primary ovarian insufficiency; FX-associated tremor/ataxia syndrome; fragile X syndrome