caa a22 4500 475845242 CHVBK 20180406123912.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/PL00000734 doi (NATIONALLICENCE)springer-10.1007/PL00000734 DNA repeat expansions and human disease [Elektronische Daten] [K. Usdin*, E. Grabczyk] Abstract.: The repeat expansion diseases are genetic disorders caused by intergenerational expansions of a specific tandem DNA repeat. These disorders range from mildly to severely debilitating or fatal, and all have limited treatment options. How expansion occurs and causes disease is only now beginning to be understood. Efforts to model expansion in mice have so far met with only limited success, perhaps due to a requirement for specific cis- or trans-acting factors. In vitro studies and data from bacteria and yeast suggest that in addition to secondary structures formed by the repeats, components of the DNA replication and recombination machinery are important determinants of instability. The consequences of expansion differ depending on where in the gene the repeat tract is located, and range from reduction of transcription initiation to protein toxicity. Recent advances are beginning to make rational approaches to the development of therapies possible. Birkhäuser Verlag Basel,, 2000 Key words. Repeat expansion nationallicence DNA instability nationallicence DNA structure nationallicence triplet repeats nationallicence polyglutamine toxicity nationallicence Usdin* K. 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), Fax +1 301 402 0053, e-mail: ku@helix.nih.gov, US aut Grabczyk E. 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), Fax +1 301 402 0053, e-mail: ku@helix.nih.gov, US aut https://doi.org/10.1007/PL00000734 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000734 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Usdin* K. 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), Fax +1 301 402 0053, e-mail: ku@helix.nih.gov, US aut NATIONALLICENCE 700 1- Grabczyk E. 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), Fax +1 301 402 0053, e-mail: ku@helix.nih.gov, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer