Unravelling molecular mechanisms in transcription-coupled nucleotide excision repair

Weegen, Y. van der (2022)

Doctoral Thesis

The cellular response to transcription-blocking DNA lesions involves the stalling of elongating RNA Polymerase II (RNAPIIo) at the lesion as well as a global shutdown of transcription. The stalling of RNAPIIo at such lesions initiates the transcription-coupled nucleotide excision repair pathway (TCR) to efficiently remove the damage and restore transcription. The TCR proteins, CSB, CSA, and UVSSA, are essential for the repair of transcription-blocking DNA lesions, but how the interplay between these proteins targets the core repair machinery, including the TFIIH complex, to lesion stalled RNAPIIo remains largely unknown.
Here, we demonstrate a sequential and highly cooperative assembly of TCR proteins and unveil the mechanism for TFIIH recruitment to DNA damage-stalled RNAPIIo. Importantly, we identified the previously uncharacterized ELOF1 gene as a core TCR factor with an additional role in preventing DNA damage during DNA replication. 

• Nucleotide excision repair
• DNA damage
• Transcription
• Replication
• Ubiquitylation

• All authors: Weegen, Y. van der
• Supervisor: Maarel, S.M. van der
• Co-supervisor: Luijsterburg, M.S.
• Committee: Attikum, H. van; Vertegaal, A.C.O.; Jacobs, J.; Marteijn, J.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-02-17
• ISBN (print): 9789464216172