eprintid: 17692
rev_number: 11
eprint_status: archive
userid: 1469
dir: disk0/00/01/76/92
datestamp: 2014-11-18 08:04:15
lastmod: 2014-11-27 11:43:54
status_changed: 2014-11-18 08:04:15
type: doctoralThesis
metadata_visibility: show
creators_name: Male, Gary
title: Insights into the Architecture of Transcription Factor IIIC
subjects: ddc-500
divisions: i-140001
adv_faculty: af-14
abstract: Transcription Factor IIIC (TFIIIC) is a six-subunit protein complex that recognises highly conserved promoter elements within genes transcribed by RNA polymerase III. These promoter elements, called ‘A box’ and ‘B box’, are recognised by two subcomplexes of TFIIIC, termed ‘τA’ and ‘τB’. The τA subcomplex is formed from three subunits: τ131, τ95 and τ55. The τB subcomplex is also composed of three subunits: τ138, τ91 and τ60. The binding of TFIIIC to these promoter elements leads to the recruitment of another transcription factor, TFIIIB, which subsequently coordinates the recruitment of RNA polymerase III to the transcription start site. 
In this thesis, I present my work on the characterisation of a novel interface between the τA and τB subcomplexes, which is located between the subunits τ131 and τ138. Chemical cross-linking coupled with mass spectrometry provides evidence for an important interaction between these two essential proteins, which I have mapped in detail using biochemical, biophysical and structural methods. The structure of a highly conserved tetra-trico peptide repeat (TPR) domain within τ131 is presented and is shown to bind with high affinity to a disordered region of τ138. In addition, I present the first high resolution structure of an extended winged helix domain of τ138 that I have solved by X-ray crystallography. Finally, I present work detailing efforts to produce the TFIIIC complex recombinantly in insect cells. The work presented here will further our understanding of the architecture of TFIIIC and provide insight into TFIIIC structure and function. 

date: 2014
id_scheme: DOI
id_number: 10.11588/heidok.00017692
ppn_swb: 810685442
own_urn: urn:nbn:de:bsz:16-heidok-176925
date_accepted: 2014-09-30
advisor: HASH(0x559e37c8efb0)
language: eng
bibsort: MALEGARYINSIGHTSIN2014
full_text_status: public
citation:   Male, Gary  (2014) Insights into the Architecture of Transcription Factor IIIC.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/17692/1/Thesis_Fomatted_All_v32_submitted.pdf