scholarly journals 1TP5-04 Interaction between tetraplex structure of mouse telomeric DNA and telomeric DNA binding domains of mouse telomere binding protein Pot1(The 47th Annual Meeting of the Biophysical Society of Japan)

2009 ◽  
Vol 49 (supplement) ◽  
pp. S37
Author(s):  
Kaoru Kaneda ◽  
Hidetaka Torigoe
Keyword(s):  
Dna Binding ◽  
Annual Meeting ◽  
Binding Protein ◽  
Telomeric Dna ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Telomere Binding Protein ◽  
Biophysical Society

scholarly journals Cdc13 N-Terminal Dimerization, DNA Binding, and Telomere Length Regulation

2010 ◽  
Vol 30 (22) ◽  
pp. 5325-5334 ◽  
Author(s):  
Meghan T. Mitchell ◽  
Jasmine S. Smith ◽  
Mark Mason ◽  
Sandy Harper ◽  
David W. Speicher ◽  
...  
Keyword(s):  
Dna Binding ◽  
Telomere Length ◽  
Functional Characterization ◽  
Point Mutations ◽  
Telomeric Dna ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Length Regulation ◽  
Telomere Length Regulation

ABSTRACT The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that is directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.

scholarly journals Rhodopsin targeted transcriptional silencing by DNA-binding

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Salvatore Botta ◽  
Elena Marrocco ◽  
Nicola de Prisco ◽  
Fabiola Curion ◽  
Mario Renda ◽  
...  
Keyword(s):  
Dna Binding ◽  
Transcriptional Repression ◽  
Binding Protein ◽  
Regulatory Element ◽  
Transcriptional Silencing ◽  
Dna Binding Protein ◽  
Gain Of Function ◽  
Dna Binding Domains ◽  
Binding Domains

Transcription factors (TFs) operate by the combined activity of their DNA-binding domains (DBDs) and effector domains (EDs) enabling the coordination of gene expression on a genomic scale. Here we show that in vivo delivery of an engineered DNA-binding protein uncoupled from the repressor domain can produce efficient and gene-specific transcriptional silencing. To interfere with RHODOPSIN (RHO) gain-of-function mutations we engineered the ZF6-DNA-binding protein (ZF6-DB) that targets 20 base pairs (bp) of a RHOcis-regulatory element (CRE) and demonstrate Rho specific transcriptional silencing upon adeno-associated viral (AAV) vector-mediated expression in photoreceptors. The data show that the 20 bp-long genomic DNA sequence is necessary for RHO expression and that photoreceptor delivery of the corresponding cognate synthetic trans-acting factor ZF6-DB without the intrinsic transcriptional repression properties of the canonical ED blocks Rho expression with negligible genome-wide transcript perturbations. The data support DNA-binding-mediated silencing as a novel mode to treat gain-of-function mutations.

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