TY  - JOUR
A1  - Schmitt, Dominik R.
A1  - Kuper, Jochen
A1  - Elias, Agnes
A1  - Kisker, Caroline
T1  - The Structure of the TFIIH p34 Subunit Reveals a Von Willebrand Factor A Like Fold
JF  - PLoS ONE
N2  - RNA polymerase II dependent transcription and nucleotide excision repair are mediated by a multifaceted interplay of subunits within the general transcription factor II H (TFIIH). A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these vital cellular processes. The importance of this complex becomes further evident in the context of severe diseases like xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy, that arise from single point mutations in TFIIH subunits. Here we describe the structure of the p34 subunit of the TFIIH complex from the eukaryotic thermophilic fungus Chaetomium thermophilum. The structure revealed that p34 contains a von Willebrand Factor A (vWA) like domain, a fold which is generally known to be involved in protein-protein interactions. Within TFIIH p34 strongly interacts with p44, a positive regulator of the helicase XPD. Putative protein-protein interfaces are analyzed and possible binding sites for the p34-p44 interaction suggested.
KW  - sequence motif analysis
KW  - iodides
KW  - protein-protein interactions
KW  - protein domains
KW  - molecular structure
KW  - electron density
KW  - protein structure
KW  - crystal structure
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119471
SN  - 1932-6203
VL  - 9
IS  - 7
ER  - 
TY  - JOUR
A1  - Bangalore, Disha M.
A1  - Heil, Hannah S.
A1  - Mehringer, Christian F.
A1  - Hirsch, Lisa
A1  - Hemmen, Katharina
A1  - Heinze, Katrin G.
A1  - Tessmer, Ingrid
T1  - Automated AFM analysis of DNA bending reveals initial lesion sensing strategies of DNA glycosylases
JF  - Scientific Reports
N2  - Base excision repair is the dominant DNA repair pathway of chemical modifications such as deamination, oxidation, or alkylation of DNA bases, which endanger genome integrity due to their high mutagenic potential. Detection and excision of these base lesions is achieved by DNA glycosylases. To investigate the remarkably high efficiency in target site search and recognition by these enzymes, we applied single molecule atomic force microscopy (AFM) imaging to a range of glycosylases with structurally different target lesions. Using a novel, automated, unbiased, high-throughput analysis approach, we were able to resolve subtly different conformational states of these glycosylases during DNA lesion search. Our results lend support to a model of enhanced lesion search efficiency through initial lesion detection based on altered mechanical properties at lesions. Furthermore, its enhanced sensitivity and easy applicability also to other systems recommend our novel analysis tool for investigations of diverse, fundamental biological interactions.
KW  - atomic-force microscopy
KW  - base pairs
KW  - molecular structure
KW  - crystal structure
KW  - structural basis
KW  - repair
KW  - recognition
KW  - 8-oxoguanine
KW  - thymine
KW  - mismatches
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231338
VL  - 10
ER  -