Nucleotide excision repair driven by the dissociation of CAK from TFIIH.
The transcription/DNA repair factor TFIIH is organized into a core that associates with the CDK-activating kinase (CAK) complex. Using chromatin immunoprecipitation, we have followed the composition of TFIIH over time after UV irradiation of repair-proficient or -deficient human cells. We show that TFIIH changes subunit composition in response to DNA damage. The CAK is released from the core during nucleotide excision repair (NER). Using reconstituted in vitro NER assay, we show that XPA catalyzes the detachment of the CAK from the core, together with the arrival of the other NER-specific factors. The release of the CAK from the core TFIIH promotes the incision/excision of the damaged oligonucleotide and thereby the repair of the DNA. Following repair, the CAK reappears with the core TFIIH on the chromatin, together with the resumption of transcription. Our findings demonstrate that the composition of TFIIH is dynamic to adapt its engagement in distinct cellular processes.
Coin
Frédéric
F
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Functional Genomics, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C.U. Strasbourg, France. fredr@igbmc.u-strasbg.fr
Oksenych
Valentyn
V
Mocquet
Vincent
V
Groh
Stefanie
S
Blattner
Christine
C
Egly
Jean Marc
JM
D000255:Adenosine Triphosphate / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008954:Models, Biological; D051758:Transcription Factor TFIIH / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000378:metabolism; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D018797:Cell Cycle Proteins; D051760:Xeroderma Pigmentosum Group A Protein; D051758:Transcription Factor TFIIH; D000255:Adenosine Triphosphate; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase