Karen Usdin

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia
    Eriko Greene
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 35:3383-90. 2007
  2. pmc ATR protects the genome against CGG.CCG-repeat expansion in Fragile X premutation mice
    Ali Entezam
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 36:1050-6. 2008
  3. pmc ATM and ATR protect the genome against two different types of tandem repeat instability in Fragile X premutation mice
    Ali Entezam
    Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 37:6371-7. 2009
  4. pmc SIRT1 inhibition alleviates gene silencing in Fragile X mental retardation syndrome
    Rea Biacsi
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 4:e1000017. 2008
  5. pmc Is Friedreich ataxia an epigenetic disorder?
    Daman Kumari
    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, MD 20892 0830, USA
    Clin Epigenetics 4:2. 2012
  6. pmc NGG-triplet repeats form similar intrastrand structures: implications for the triplet expansion diseases
    K Usdin
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 26:4078-85. 1998
  7. pmc The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome
    Daman Kumari
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Disease NIH, Bethesda, MD 20892 0830, USA
    Hum Mol Genet 19:4634-42. 2010
  8. ncbi request reprint DNA repeat expansions and human disease
    K Usdin
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    Cell Mol Life Sci 57:914-31. 2000
  9. pmc The biological effects of simple tandem repeats: lessons from the repeat expansion diseases
    Karen Usdin
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    Genome Res 18:1011-9. 2008
  10. pmc The role of DNA damage response pathways in chromosome fragility in Fragile X syndrome
    Daman Kumari
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 37:4385-92. 2009

Collaborators

  • Gloria E Hoffman
  • Mirit I Aladjem
  • Robert L Nussbaum
  • William M Bonner
  • E Grabczyk
  • Asako J Nakamura
  • Peter McPhie
  • Tapas Saha
  • Daman Kumari
  • Ali Entezam
  • Rachel Adihe Lokanga
  • Dmitry Yudkin
  • Vaishali Handa
  • Mei Qin
  • Eriko Greene
  • Rea Biacsi
  • Lata Mahishi
  • D Kumari
  • Xiao Nan Zhao
  • K Fleming
  • E Greene
  • Bruce E Hayward
  • Carolyn Beebe Smith
  • Rachel Lokanga
  • Zhong Hua Liu
  • Carolyn B Smith
  • Tianjian Huang
  • Rea Erika Biacsi
  • Wei Le
  • Adihe Rachel Lokanga
  • Valentina Somma
  • Ettore D'Ambrosio
  • Bonnie Orrison
  • David Wheeler
  • Herman J C Yeh
  • Andrei Gabrielian
  • Deena Goldwater
  • George Poy
  • Margaret Cam
  • David Stiles
  • E L Cabot
  • V Handa
  • D K Riser
  • B Angeletti
  • A V Furano

Detail Information

Publications33

  1. pmc Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia
    Eriko Greene
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 35:3383-90. 2007
    ..Our results also raise the possibility that the repeat-mediated increases in DNA methylation in the FXN gene in FRDA patients are secondary to the chromatin changes...
  2. pmc ATR protects the genome against CGG.CCG-repeat expansion in Fragile X premutation mice
    Ali Entezam
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 36:1050-6. 2008
    ..In addition, our data provide an explanation for the maternal bias of large expansions in humans and the lower incidence of these expansions in mice...
  3. pmc ATM and ATR protect the genome against two different types of tandem repeat instability in Fragile X premutation mice
    Ali Entezam
    Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 37:6371-7. 2009
    ..Our data thus support the hypothesis that two different mechanisms of FX repeat expansion exist, an ATR-sensitive mechanism seen on maternal transmission and an ATM-sensitive mechanism that shows a male expansion bias...
  4. pmc SIRT1 inhibition alleviates gene silencing in Fragile X mental retardation syndrome
    Rea Biacsi
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 4:e1000017. 2008
    ....
  5. pmc Is Friedreich ataxia an epigenetic disorder?
    Daman Kumari
    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, MD 20892 0830, USA
    Clin Epigenetics 4:2. 2012
    ..This review discusses evidence for and against different models for the repeat-mediated mRNA deficit...
  6. pmc NGG-triplet repeats form similar intrastrand structures: implications for the triplet expansion diseases
    K Usdin
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 26:4078-85. 1998
    ....
  7. pmc The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome
    Daman Kumari
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Disease NIH, Bethesda, MD 20892 0830, USA
    Hum Mol Genet 19:4634-42. 2010
    ..This suggests that the trigger for gene silencing may be local to the repeat itself and perhaps involves a mechanism similar to that involved in the formation of pericentric heterochromatin...
  8. ncbi request reprint DNA repeat expansions and human disease
    K Usdin
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    Cell Mol Life Sci 57:914-31. 2000
    ..Recent advances are beginning to make rational approaches to the development of therapies possible...
  9. pmc The biological effects of simple tandem repeats: lessons from the repeat expansion diseases
    Karen Usdin
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    Genome Res 18:1011-9. 2008
    ....
  10. pmc The role of DNA damage response pathways in chromosome fragility in Fragile X syndrome
    Daman Kumari
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 37:4385-92. 2009
    ..FRAXA also displays a second form of chromosome fragility in absence of FdU, which our data suggest is normally prevented by an ATM-dependent process...
  11. pmc Somatic expansion in mouse and human carriers of fragile X premutation alleles
    Rachel Adihe Lokanga
    Section on Gene Structure and Disease, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    Hum Mutat 34:157-66. 2013
    ..This could explain, at least in part, the variable penetrance seen in some of these disorders...
  12. pmc Chromatin changes in the development and pathology of the Fragile X-associated disorders and Friedreich ataxia
    Daman Kumari
    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, MD 20892 0830, USA
    Biochim Biophys Acta 1819:802-10. 2012
    ..This review will address the role of repeat-mediated chromatin changes in these aspects of FXD and FRDA disease pathology. This article is part of a Special Issue entitled: Chromatin in time and space...
  13. pmc Regional FMRP deficits and large repeat expansions into the full mutation range in a new Fragile X premutation mouse model
    Ali Entezam
    Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, United States
    Gene 395:125-34. 2007
    ....
  14. pmc Repeat expansion affects both transcription initiation and elongation in friedreich ataxia cells
    Daman Kumari
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    J Biol Chem 286:4209-15. 2011
    ..Our findings may have implications for understanding the mechanism responsible for FRDA as well as for therapeutic approaches to reverse the transcription deficit...
  15. ncbi request reprint The AUUCU repeats responsible for spinocerebellar ataxia type 10 form unusual RNA hairpins
    Vaishali Handa
    Laboratory of Molecular and Cellular Biology, National Institutes of Health, Bethesda, MD 20892 0830, USA
    J Biol Chem 280:29340-5. 2005
    ..Thus the ability to form an RNA hairpin seems to be a common property of those Repeat Expansion Diseases that are not recessively inherited and are caused by repeats that are transcribed but not translated...
  16. ncbi request reprint Long CGG-repeat tracts are toxic to human cells: implications for carriers of Fragile X premutation alleles
    Vaishali Handa
    Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    FEBS Lett 579:2702-8. 2005
    ..We show here that long transcribed but untranslated CGG-repeat tracts are toxic to human cells and alter the expression of a wide variety of different genes including caspase-8, CYFIP, Neurotensin and UBE3A...
  17. ncbi request reprint Ancient repeated DNA elements and the regulation of the human frataxin promoter
    Eriko Greene
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Genomics 85:221-30. 2005
    ....
  18. pmc NF-Y, AP2, Nrf1 and Sp1 regulate the fragile X-related gene 2 (FXR2)
    Lata Mahishi
    Gene Structure and Disease Section, NIDDK National Institute of Diabetes and Digestive and Kidney Diseases, NIH National Institutes of Health, Bethesda, MD 20892 0830, USA
    Biochem J 400:327-35. 2006
    ....
  19. pmc Chromatin remodeling in the noncoding repeat expansion diseases
    Daman Kumari
    Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    J Biol Chem 284:7413-7. 2009
    ....
  20. pmc The roles of Sp1, Sp3, USF1/USF2 and NRF-1 in the regulation and three-dimensional structure of the Fragile X mental retardation gene promoter
    Daman Kumari
    National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Biochem J 386:297-303. 2005
    ..We can reconcile these observations with the positive effect of Sp1 and Sp3 if protein-induced bending acts, at least in part, to bring together distally spaced factors important for transcription initiation...
  21. pmc Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model
    Ali Entezam
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, MD 20892, USA
    Hum Mutat 31:611-6. 2010
    ..We show here that KBrO(3) increased both the level of 8-oxoG in the oocytes of treated animals and the germline expansion frequency. Our data thus suggest that oxidative damage may be a factor that could affect expansion risk in humans...
  22. pmc A mouse model of the fragile X premutation: effects on behavior, dendrite morphology, and regional rates of cerebral protein synthesis
    Mei Qin
    Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
    Neurobiol Dis 42:85-98. 2011
    ..Our results highlight similarities in phenotype between KI and Fmr1 knockout mice and suggest that the decreased concentration of FMRP contributes to the phenotype in young adult KI mice...
  23. ncbi request reprint Transcription defects induced by repeat expansion: fragile X syndrome, FRAXE mental retardation, progressive myoclonus epilepsy type 1, and Friedreich ataxia
    E Greene
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Cytogenet Genome Res 100:65-76. 2003
    ..In this review, we discuss current models for the relationship between the expanded repeat and the disease symptoms...
  24. pmc The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer
    Vaishali Handa
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 31:6243-8. 2003
    ..In addition, RNA hairpins may also account for the stalling of the 40S ribosomal subunit that is thought to contribute to the translation deficit in fragile X pre-mutation and full mutation alleles...
  25. pmc Alleviating transcript insufficiency caused by Friedreich's ataxia triplet repeats
    E Grabczyk
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 28:4930-7. 2000
    ..In principle, therapeutic agents that selectively interfere with triplex formation could alleviate the frataxin transcript insufficiency caused by pathogenic FRDA alleles...
  26. pmc The GAA*TTC triplet repeat expanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner
    E Grabczyk
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 28:2815-22. 2000
    ..The non-template (GAA) strand folds back creating a loop in the template strand, and the polymerase is paused at the distal triplex-duplex junction...
  27. ncbi request reprint Tetraplex formation by the progressive myoclonus epilepsy type-1 repeat: implications for instability in the repeat expansion diseases
    T Saha
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Kidney Diseases, Building 8, Room 202, National Institutes of Health, 8 CENTER DR MSC 0830, Bethesda, MD 20892 0830, USA
    FEBS Lett 491:184-7. 2001
    ..However, EPM1 is unique in that tetraplexes are the only structures likely to form in long unpaired repeat tracts under physiological conditions...
  28. ncbi request reprint X inactivation plays a major role in the gender bias in somatic expansion in a mouse model of the fragile X-related disorders: implications for the mechanism of repeat expansion
    Rachel Adihe Lokanga
    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, MD 20892, USA and Department of Medical Biochemistry, University of Cape Town, Cape Town, South Africa
    Hum Mol Genet . 2014
    ..The fact that expansion only occurs when the Fmr1 allele is on the active X chromosome has important implications for the mechanism of repeat expansion...
  29. ncbi request reprint Chromosome fragility and the abnormal replication of the FMR1 locus in fragile X syndrome
    Dmitry Yudkin
    Section on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, and
    Hum Mol Genet 23:2940-52. 2014
    ..Our data on FRAXA may also be germane for the other FdU-inducible fragile sites in humans, that we show here share many common features with FRAXA. ..
  30. ncbi request reprint Instability of the fragile X syndrome repeat in mice: the effect of age, diet and mutations in genes that affect DNA replication, recombination and repair proficiency
    K Fleming
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Cytogenet Genome Res 100:140-6. 2003
    ..Moreover, the fact that contractions occur in the absence of expansions suggests that these processes occur by different mechanisms...
  31. ncbi request reprint Fragile X syndrome and Friedreich's ataxia: two different paradigms for repeat induced transcript insufficiency
    E Grabczyk
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA
    Brain Res Bull 56:367-73. 2001
    ..purine. pyrimidine DNA triplex behind an advancing RNA polymerase. This structure lassoes the RNA polymerase that caused it, trapping the enzyme on the template...
  32. ncbi request reprint Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome
    D Kumari
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    J Biol Chem 276:4357-64. 2001
    ..This suggests that for efficient reactivation of the FMR1 promoter, significant demethylation must occur and that current approaches to gene reactivation using histone deacetylase inhibitors alone may therefore have limited effect...
  33. ncbi request reprint Rapid evolution of a young L1 (LINE-1) clade in recently speciated Rattus taxa
    E L Cabot
    Section on Genomic Structure and Function, NIDDK, NIH, Bethesda, MD 20892 0830, USA
    J Mol Evol 45:412-23. 1997
    ....