|
Cockayne Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mapping disease mutations associated with xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome onto defined communities reveals clustering into three mechanistic classes that affect TFIIH helicase functions, protein interactions and interface dynamics.
|
31110295 |
2019 |
|
Xeroderma Pigmentosum
|
0.100 |
Biomarker
|
disease |
BEFREE |
TFIIH multi-protein complex with its important helicase-Xeroderma Pigmentosum Protein (XPD) serves as the pivotal factor for opening up of the damaged lesion DNA site and carry out the repair process.
|
29616226 |
2018 |
|
Trichothiodystrophy Syndromes
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Using quantitative imaging of TFIIH in living mouse cells, we found that these molecules reduce the intracellular concentration of TFIIH and its transcriptional activity to levels similar to that observed in individuals with trichothiodystrophy owing to mutated <i>TTD-A</i> Our results provide a proof of concept of fragment-based drug discovery, demonstrating the utility of small molecules for targeting p8 dimerization to modulate the transcriptional machinery, an approach that may help inform further development in anticancer therapies.
|
30068551 |
2018 |
|
Xeroderma Pigmentosum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
This provides first insights why so far no mutations in the p34 or p44 TFIIH-core subunits have been identified that would lead to the hallmark nucleotide excision repair syndromes xeroderma pigmentosum or trichothiodystrophy.
|
28977422 |
2017 |
|
Cockayne Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results suggest that the XPG-TFIIH complex is involved in transcription elongation and that defects in this association may partly account for Cockayne syndrome in XP-G/CS patients.
|
26149386 |
2015 |
|
Xeroderma Pigmentosum
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in distinct clinical entities, including the cancer-prone xeroderma pigmentosum (XP) and the multisystem disorder trichothiodystrophy (TTD), which share only cutaneous photosensitivity.
|
25605938 |
2015 |
|
Xeroderma Pigmentosum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.
|
25620205 |
2015 |
|
Trichothiodystrophy Syndromes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.
|
25620205 |
2015 |
|
Trichothiodystrophy Syndromes
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
TFIIH-dependent MMP-1 overexpression in trichothiodystrophy leads to extracellular matrix alterations in patient skin.
|
25605938 |
2015 |
|
Trichothiodystrophy Syndromes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
To further grasp the molecular mechanisms that govern transcription, we focused our attention on the general transcription factor TFIIH, which gives rise, once mutated, to Trichothiodystrophy (TTD), a rare autosomal premature-ageing disease causing inter alia, metabolic dysfunctions.
|
25340339 |
2014 |
|
Cockayne Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Moreover, mutations in the TFIIH subunits XPB and XPD found in Cockayne syndrome impair the interaction of TFIIH with the rDNA, but do not influence initiation complex formation or promoter escape of RNA polymerase I, but preclude the productivity of the enzyme by reducing transcription elongation in vivo and in vitro.
|
21965540 |
2012 |
|
Xeroderma Pigmentosum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Our results suggested a link between TTD- but not XP-associated XPD mutations, placental maldevelopment and risk of pregnancy complications, possibly due to impairment of TFIIH-mediated functions in placenta.
|
22234153 |
2012 |
|
Trichothiodystrophy Syndromes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Our results suggested a link between TTD- but not XP-associated XPD mutations, placental maldevelopment and risk of pregnancy complications, possibly due to impairment of TFIIH-mediated functions in placenta.
|
22234153 |
2012 |
|
Xeroderma Pigmentosum
|
0.100 |
Biomarker
|
disease |
BEFREE |
This integration resolves puzzles regarding XP helicase functions and suggests that XP helicase positions and activities within TFIIH detect and verify damage, select the damaged strand for incision, and coordinate repair with transcription and cell cycle through CAK signaling.
|
21571596 |
2011 |
|
Trichothiodystrophy Syndromes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
TTD group A (TTD-A) patients carry mutations in the smallest TFIIH subunit, TTDA, which is an 8-kDa protein that dynamically interacts with TFIIH.
|
21730288 |
2011 |
|
Trichothiodystrophy Syndromes
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Ongoing investigations on TTD are elucidating not only the pathogenesis of the disease, which appears to be mainly related to transcriptional impairment, but also the modalities of NER and transcription in human cells and how TFIIH operates in these two fundamental cellular processes.
|
19931493 |
2010 |
|
Xeroderma Pigmentosum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in the rare recessive genetic disorder xeroderma pigmentosum (XP).
|
19934020 |
2009 |
|
Trichothiodystrophy Syndromes
|
0.100 |
Biomarker
|
disease |
BEFREE |
Moreover, mutations in any of these three TFIIH subunits also disturb the overall architecture of the TFIIH complex and its ability to transactivate certain nuclear receptor-responsive genes, explaining in part, some of the TTD phenotypes.
|
19808800 |
2009 |
|
Cockayne Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
A recent report provides a molecular basis for how mutations in the NER endonuclease XPG that affect the interaction of TFIIH might give rise to CS features.
|
18077223 |
2008 |
|
Cockayne Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mutations in certain subunits of the DNA repair/transcription factor complex TFIIH are linked to the human syndromes xeroderma pigmentosum (XP), Cockayne's syndrome (CS), and trichothiodystrophy (TTD).
|
19008953 |
2008 |
|
Xeroderma Pigmentosum
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Mutations in certain subunits of the DNA repair/transcription factor complex TFIIH are linked to the human syndromes xeroderma pigmentosum (XP), Cockayne's syndrome (CS), and trichothiodystrophy (TTD).
|
19008953 |
2008 |
|
Xeroderma Pigmentosum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Accordingly, defects in specific enzymatic functions typically result in XP, dissociation of the CAK subunit from TFIIH is associated with XP/CS and a more generalized destabilization of TFIIH gives rise to TTD.
|
18077223 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.100 |
Biomarker
|
disease |
BEFREE |
Accordingly, defects in specific enzymatic functions typically result in XP, dissociation of the CAK subunit from TFIIH is associated with XP/CS and a more generalized destabilization of TFIIH gives rise to TTD.
|
18077223 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
p8/TTDA overexpression enhances UV-irradiation resistance and suppresses TFIIH mutations in a Drosophila trichothiodystrophy model.
|
19008953 |
2008 |
|
Trichothiodystrophy Syndromes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Patients with the rare neurodevelopmental repair syndrome known as group A trichothiodystrophy (TTD-A) carry mutations in the gene encoding the p8 subunit of the transcription and DNA repair factor TFIIH.
|
19172752 |
2008 |