The sequential and cooperative action of CSB, CSA and UVSSA targets the TFIIH complex to DNA damage-stalled RNA polymerase II

Yana van der Weegen, Hadar Golan Berman, Tycho E.T. Mevissen, Katja Apelt, Román González-Prieto, Elisheva Heilbrun, Alfred C.O. Vertegaal, Diana van den Heuvel, Johannes C. Walter, Sheera Adar, and Martijn S. Luijsterburg

Jul 22, 2019
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Received Date: 2nd July 19

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 reveal 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.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

 

Nature Communications

Nature Research, Springer Nature