Gender and cell-type-specific effects of the transcription-coupled repair protein, ERCC6/CSB, on repeat expansion in a mouse model of the fragile X-related disorders

Human Mutation
Xiao-Nan Zhao, Karen Usdin

Abstract

The repeat expansion diseases are human genetic disorders that arise from the expansion of a tandem-repeat tract. The Fragile X-related disorders are members of this disease group in which the repeat unit is CGG/CCG and is located in the 5′ untranslated region of the FMR1 gene. Affected individuals often show mosaicism with respect to repeat number resulting from both expansion and contraction of the repeat tract; however, the mechanism responsible for these changes in repeat number is unknown. The work from a variety of model systems suggests that transcription-coupled repair (TCR) may contribute to repeat instability in diseases resulting from CAG/CTG-repeat expansion. To test whether TCR could contribute to repeat instability in the Fragile X-related disorders, we tested the effect of mutations in Csb (Cockayne syndrome group B), a gene essential for TCR, in a knock-in mouse model of these disorders. We found that the loss of CSB affects expansions in a gender and cell-type-specific manner. Our data also show an unanticipated gender difference in instability even in Csb+/+ animals that may have implications for our understanding of the mechanism of repeat expansion in the FX mouse model and perhaps for humans as well.

References

Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·C P Selby, A Sancar
Jan 15, 1999·Human Molecular Genetics·V C WheelerM E MacDonald
Jan 13, 2000·American Journal of Human Genetics·F TassoneP J Hagerman
Mar 10, 2001·Molecular Reproduction and Development·W J Murdoch, E A Van Kirk
Jul 14, 2001·American Journal of Medical Genetics·S L Sherman
Jan 1, 1997·Apoptosis : an International Journal on Programmed Cell Death·W J Murdoch, E A Van Kirk
Feb 6, 2004·The Journal of Biological Chemistry·Varsha S LikhiteAnn M Nardulli
Mar 3, 2004·Mental Retardation and Developmental Disabilities Research Reviews·Paul J Hagerman, Randi J Hagerman
Oct 6, 2005·Nature Reviews. Genetics·Christopher E PearsonJohn D Cleary
May 23, 2006·Current Opinion in Structural Biology·Sergei M Mirkin
Jun 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·John C NewmanAlan M Weiner
Jan 17, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Charles M StromWeimin Sun
Mar 3, 2007·Seminars in Pediatric Neurology·Richard E Lutz
Apr 10, 2007·Annual Review of Neuroscience·Harry T Orr, Huda Y Zoghbi
Dec 28, 2007·Nucleic Acids Research·Ali Entezam, Karen Usdin
Nov 1, 2008·Molecular Carcinogenesis·Yunfu LinJohn H Wilson
Jan 31, 2009·The Journal of Biological Chemistry·Meltem MuftuogluVilhelm A Bohr
Mar 23, 2010·BMC Systems Biology·Jong-Min LeeVanessa C Wheeler
Mar 5, 2011·Trends in Endocrinology and Metabolism : TEM·Jennifer R Schultz-NortonAnn M Nardulli
Jun 10, 2011·Clinical Genetics·R WillemsenB A Oostra
Jun 15, 2011·Nucleic Acids Research·Viviana Salinas-RiosPhilip C Hanawalt
Jul 13, 2012·The Journal of Biological Chemistry·Anasheh HalabiEd Grabczyk
Aug 14, 2012·Human Mutation·Rachel Adihe LokangaKaren Usdin

❮ Previous
Next ❯

Citations

Jan 23, 2015·Critical Reviews in Biochemistry and Molecular Biology·Karen UsdinCatherine H Freudenreich
May 24, 2015·DNA Repair·Xiao-Nan Zhao, Karen Usdin
Feb 16, 2020·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin
Aug 1, 2018·Nature Structural & Molecular Biology·Artem V KononenkoSergei M Mirkin
Mar 31, 2018·Frontiers in Molecular Neuroscience·Regina Dahlhaus
Jan 29, 2021·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin

❮ 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.