DNA lesions that block transcription may cause cell death even when repaired, if transcription does not restart to reestablish cellular metabolism. However, transcription resumption after individual DNA-lesion repair remains poorly described in mechanistic terms and its players are largely unknown. The general transcription factor II H (TFIIH) is a major actor of both nucleotide excision repair subpathways of which transcription-coupled repair highlights the interplay between DNA repair and transcription. Using an unbiased proteomic approach, we have identified the protein eleven-nineteen lysine-rich leukemia (ELL) as a TFIIH partner. Here we show that ELL is recruited to UV-damaged chromatin in a Cdk7-dependent manner (a component of the cyclin-dependent activating kinase subcomplex of TFIIH). We demonstrate that depletion of ELL strongly hinders RNA polymerase II (RNA Pol II) transcription resumption after lesion removal and DNA gap filling. Lack of ELL was also observed to increase RNA Pol II retention to the chromatin during this process. Identifying ELL as an essential player for RNA Pol II restart during cellular DNA damage response opens the way to obtaining a mechanistic description of transcription resumption after DNA repair.elongation factor | CAK | LEC | Cockayne syndrome | TCR D amage to DNA induced by UV irradiation is repaired by the nucleotide excision repair (NER) system. Three DNA repair-deficient disorders emphasize the importance of NER in genome stability (1). In eukaryotic cells, NER can be divided into two pathways: global genome repair (GGR), repairing lesions throughout the genome, and transcription-coupled repair (TCR), which repairs lesions on the transcribed strand of active genes (2). After damage detection, the basal transcription/repair factor II H (TFIIH), containing the XPB and XPD ATPase/helicases is needed to locally unwind the DNA double helix around the lesion. Furthermore, in vitro UV irradiation elicits a change in the composition of TFIIH. Indeed the majority of TFIIH present on UV-damaged chromatin does not contain the ternary cyclindependent activating kinase (CAK) complex (3). More specifically, the CAK complex is found to be only implicated in TCR but not during GGR, where it seems to be released from the remaining TFIIH components, concomitantly with the recruitment of subsequent NER factors (3). To better our understanding of TFIIH functions in vivo, we have used a combination of improved immunoprecipitation assays and proteomic analysis to identify and characterize TFIIH-interacting partners.Our quantitative proteomic approach has identified several putative TFIIH partners, of which the four most enriched constitute the Little Elongation Complex (LEC): eleven-nineteen lysinerich leukemia (ELL), EAF1 (ELL-associated factor 1), KIAA0947, and NARG2 (4). The proposed role of the LEC is to regulate the transcription of small nuclear RNA genes (5). Although ELL and EAF1 are also part of the Super Elongation Complex (SEC), known to regulate the transcriptional elongation c...

A novel mouse model reveals that the dynamic behavior of transcription factors can vary considerably between different cells of an organism.