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유전체 항상성 연구단
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Envisioning how the prototypic molecular machine TFIIH functions in transcription initiation and DNA repair

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Title
Envisioning how the prototypic molecular machine TFIIH functions in transcription initiation and DNA repair
Author(s)
Susan E. Tsutakawa; Chi-Lin Tsai; Chunli Yan; Amer Brali´c; Walter J. Chazin; Samir M. Hamdan; Orlando D. Sch¨arer; Ivaylo Ivanov; John A. Tainer
Publication Date
2020-12
Journal
DNA REPAIR, v.96, pp.102972
Publisher
ELSEVIER SCIENCE BV
Abstract
Critical for transcription initiation and bulky lesion DNA repair, TFIIH provides an exemplary system to connect molecular mechanisms to biological outcomes due to its strong genetic links to different specific human diseases. Recent advances in structural and computational biology provide a unique opportunity to re-examine biologically relevant molecular structures and develop possible mechanistic insights for the large dynamic TFIIH complex. TFIIH presents many puzzles involving how its two SF2 helicase family enzymes, XPB and XPD, function in transcription initiation and repair: how do they initiate transcription, detect and verify DNA damage, select the damaged strand for incision, coordinate repair with transcription and cell cycle through Cdk-activating-kinase (CAK) signaling, and result in very different specific human diseases associated with cancer, aging, and development from single missense mutations? By joining analyses of breakthrough cryo-electron microscopy (cryo-EM) structures and advanced computation with data from biochemistry and human genetics, we develop unified concepts and molecular level understanding for TFIIH functions with a focus on structural mechanisms. We provocatively consider that TFIIH may have first evolved from evolutionary pressure for TCR to resolve arrested transcription blocks to DNA replication and later added its key roles in transcription initiation and global DNA repair. We anticipate that this level of mechanistic information will have significant impact on thinking about TFIIH, laying a robust foundation suitable to develop new paradigms for DNA transcription initiation and repair along with insights into disease prevention, susceptibility, diagnosis and interventions
URI
https://pr.ibs.re.kr/handle/8788114/7523
DOI
10.1016/j.dnarep.2020.102972
ISSN
1568-7864
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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