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The double edged sword of DNA repair
Author(s) -
Kisker Caroline,
Kuper Jochen,
Braun Cathy,
Elias Agnes,
Michels Gudrun,
Poterszman Arnaud,
Egly JeanMarc
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.389.1
Subject(s) - transcription factor ii h , helicase , nucleotide excision repair , dna repair , transcription (linguistics) , transcription factor ii a , rna helicase a , biology , rna polymerase ii , rna polymerase ii holoenzyme , general transcription factor , microbiology and biotechnology , dna , computational biology , chemistry , polymerase , genetics , promoter , rna , gene , rna dependent rna polymerase , gene expression , linguistics , philosophy
Two fundamental processes, RNA polymerase II dependent transcription and nucleotide excision DNA repair (NER) are linked by the multi‐protein complex TFIIH. This transcription factor consists of a total of ten subunits of which XPB, p62, p52, p44, p34, and p8 build the core and cdk7, MAT1, and cyclin H comprise an additional regulatory unit called the CAK complex; both subcomplexes are bridged by the helicase XPD. We aim to decipher the different functionalities of the individual subunits and their interplay leading to the required enzymatic activities to permit transcription and repair. Our studies show that XPD assumes entirely different functionalities in both processes. For repair the enzymatic activities are essential. In contrast, none of XPDs enzymatic functions are required for transcription and XPD switches from an enzyme to a structural protein merely preserving TFIIH integrity. We thus have shown that the XPD helicase is exclusively devoted to repair processes and could be targeted by drugs without affecting transcription. XPD might therefore represent an excellent surrogate drug target for cancer therapy approaches using DNA damaging agents like cisplatin. We are now in the process of analyzing the other core subunits within TFIIH aiming to decipher their roles in transcription and repair.Model of the different helicase functionalities in NER and transcription