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Nat Commun January 1, 2020; 11 (1): 2104.
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The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II.

van der Weegen Y , Golan-Berman H , Mevissen TET , Apelt K , González-Prieto R , Goedhart J , Heilbrun EE , Vertegaal ACO , van den Heuvel D , Walter JC , Adar S , Luijsterburg MS .

The response to DNA damage-stalled RNA polymerase II (RNAPIIo) involves the assembly of the transcription-coupled repair (TCR) complex on actively transcribed strands. The function of the TCR proteins CSB, CSA and UVSSA and the manner in which the core DNA repair complex, including transcription factor IIH (TFIIH), is recruited are largely unknown. Here, we define the assembly mechanism of the TCR complex in human isogenic knockout cells. We show that TCR is initiated by RNAPIIo-bound CSB, which recruits CSA through a newly identified CSA-interaction motif (CIM). Once recruited, CSA facilitates the association of UVSSA with stalled RNAPIIo. Importantly, we find that UVSSA is the key factor that recruits the TFIIH complex in a manner that is stimulated by CSB and CSA. Together these findings identify a sequential and highly cooperative assembly mechanism of TCR proteins and reveal the mechanism for TFIIH recruitment to DNA damage-stalled RNAPIIo to initiate repair.

PubMed ID: 32355176
PMC ID: PMC7192910
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cir1 cpd cul4a ddb1 ercc6 gtf2h4 hspa9 isyna1 rbx1 xpa xpc

Article Images: [+] show captions
References [+] :
Adar, Genome-wide kinetics of DNA excision repair in relation to chromatin state and mutagenesis. 2017, Pubmed