Splitting hairs – discovery of a new DNA repair and transcription factor for the human disease trichothiodystrophy

DNA Repair ◽  
2005 ◽  
Vol 4 (2) ◽  
pp. 285-287 ◽  
Author(s):  
James E. Cleaver
Keyword(s):  
Dna Repair ◽  
Transcription Factor ◽  
Human Disease

141 Mitochondrial transcription factor a mitochondrial DNA repair

Mitochondrion ◽  
2010 ◽  
Vol 10 (2) ◽  
pp. 240
Author(s):  
Deborah L. Croteau ◽  
Anne-Cécile V. Bayne ◽  
Chandrika Canugovi ◽  
Scott Maynard ◽  
Nadja de Souza-Pinto ◽  
...  
Keyword(s):  
Dna Repair ◽  
Transcription Factor ◽  
Mitochondrial Dna ◽  
Mitochondrial Transcription ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Dna Repair ◽  
Mitochondrial Transcription Factor A

scholarly journals Structural basis of TFIIH activation for nucleotide excision repair

2019 ◽  
Author(s):  
Goran Kokic ◽  
Aleksandar Chernev ◽  
Dimitry Tegunov ◽  
Christian Dienemann ◽  
Henning Urlaub ◽  
...  
Keyword(s):  
Dna Repair ◽  
Transcription Factor ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Dna Lesions ◽  
Structural Basis ◽  
Disease Mutations ◽  
Mechanistic Analysis ◽  
Nucleotide Excision ◽  
Dna Complex

AbstractGenomes are constantly threatened by DNA damage, but cells can remove a large variety of DNA lesions by nucleotide excision repair (NER)1. Mutations in NER factors compromise cellular fitness and cause human diseases such as Xeroderma pigmentosum (XP), Cockayne syndrome and trichothiodystrophy2,3. The NER machinery is built around the multisubunit transcription factor IIH (TFIIH), which opens the DNA repair bubble, scans for the lesion, and coordinates excision of the damaged DNA single strand fragment1,4. TFIIH consists of a kinase module and a core module that contains the ATPases XPB and XPD5. Here we prepare recombinant human TFIIH and show that XPB and XPD are stimulated by the additional NER factors XPA and XPG, respectively. We then determine the cryo-electron microscopy structure of the human core TFIIH-XPA-DNA complex at 3.6 Å resolution. The structure represents the lesion-scanning intermediate on the NER pathway and rationalizes the distinct phenotypes of disease mutations. It reveals that XPB and XPD bind double- and single-stranded DNA, respectively, consistent with their translocase and helicase activities. XPA forms a bridge between XPB and XPD, and retains the DNA at the 5’-edge of the repair bubble. Biochemical data and comparisons with prior structures6,7 explain how XPA and XPG can switch TFIIH from a transcription factor to a DNA repair factor. During transcription, the kinase module inhibits the repair helicase XPD8. For DNA repair, XPA dramatically rearranges the core TFIIH structure, which reorients the ATPases, releases the kinase module and displaces a ‘plug’ element from the DNA-binding pore in XPD. This enables XPD to move by ~80 Å, engage with DNA, and scan for the lesion in a XPG-stimulated manner. Our results provide the basis for a detailed mechanistic analysis of the NER mechanism.

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression

2016 ◽  
Vol 39 (5) ◽  
pp. 435-447 ◽  
Author(s):  
Meixiang Xu ◽  
Courtney E. Cross ◽  
Jordan T. Speidel ◽  
Sherif Z. Abdel-Rahman
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Transcription Factor ◽  
Gene Promoter ◽  
Transcription Factor Binding ◽  
Repair Gene ◽  
Factor Binding ◽  
Dna Repair Gene
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