The transcription-coupled repair protein ERCC6/CSB also protects against repeat expansion in a mouse model of the fragile X premutation

Human Mutation
Xiao-Nan Zhao, Karen Usdin

Abstract

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.

References

Jan 30, 1995·American Journal of Medical Genetics·T W PriorB G Enrile
Jul 15, 1994·American Journal of Medical Genetics·S L NolinC S Dobkin
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Fry, L A Loeb
May 20, 1999·American Journal of Medical Genetics·B Schmucker, J Seidel
May 20, 1999·American Journal of Medical Genetics·E PetekK Wagner
May 20, 1999·American Journal of Medical Genetics·E ReyniersP J Willems
Nov 20, 2001·Nucleic Acids Research·P Fojtík, M Vorlícková
May 23, 2006·Current Opinion in Structural Biology·Sergei M Mirkin
Nov 1, 2007·European Journal of Human Genetics : EJHG·Elisabetta TabolacciGiovanni Neri
Feb 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Roman GonitelGillian P Bates
Nov 26, 2008·Biochimie·Daniel RenciukMichaela Vorlícková
Dec 9, 2009·Advances in Pediatrics·Weerasak ChonchaiyaRandi J Hagerman
Feb 24, 2010·Nature Reviews. Molecular Cell Biology·Arturo López CastelChristopher E Pearson
Mar 23, 2010·BMC Systems Biology·Jong-Min LeeVanessa C Wheeler
Mar 8, 2011·Human Molecular Genetics·Stéphanie ToméChristopher E Pearson
Jul 13, 2012·The Journal of Biological Chemistry·Anasheh HalabiEd Grabczyk
Aug 14, 2012·Human Mutation·Rachel Adihe LokangaKaren Usdin
Feb 21, 2013·Mechanisms of Ageing and Development·Robert J Lake, Hua-Ying Fan
Mar 5, 2014·Journal of Medical Genetics·Dalyir I PrettoFlora Tassone
Apr 20, 2014·PLoS Genetics·Erick W LoomisPaul J Hagerman

❮ Previous
Next ❯

Citations

Jan 18, 2016·DNA Repair·Monika H M Schmidt, Christopher E Pearson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.