Nucleotide excision repair (NER) is a vital DNA repair process for bulky DNA lesions. This can occur through global-genomic NER (GG-NER) or transcription coupled NER (TC-NER). While the general mechanisms are known, the NER structure and detailed mechanism of how the bulky lesions are recognized and excised from DNA are still unclear. It is known that the general transcription factor, TFIIH, is indispensable for both transcription initiation and NER. Therefore, we use cryo-EM data to build a TFIIH-DNA-XPA model. We perform molecular dynamics simulations on this model and reveal the global motions, partition the complex into dynamic communities, and compare the apo, pre-initiation complex (PIC), and NER forms of TFIIH. The motions of the XPB and XPD helicases in the absence of ATP are identified. The comparison between the apo, PIC, and NER forms of TFIIH reveal how the conformational change must occur for TFIIH to transition from being transcription initiation ready to become DNA repair competent.

Elucidating the dynamics of TFIIH in the NER complex

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.