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The Role of TFIIH Complex in Nucleotide Excision Repair
  • Allyson Hoag,
  • Mingrui Duan,
  • Peng Mao
Allyson Hoag
University of New Mexico
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Mingrui Duan
University of New Mexico
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Peng Mao
University of New Mexico

Corresponding Author:pmao@salud.unm.edu

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Abstract

DNA damage occurs throughout life from a variety of sources, and it is imperative to repair damage in a timely manner to maintain genome stability. Thus, DNA repair mechanisms are a fundamental part of life. Nucleotide Excision Repair (NER) plays an important role in the removal of bulky DNA adducts, such as cyclobutane pyrimidine dimers (CPDs) from ultraviolet (UV) light or DNA crosslinking damage from platinum-based chemotherapeutics, such as cisplatin. A main component for the NER pathway is transcription factor IIH (TFIIH), a multifunctional, 10-subunit protein complex with crucial roles in both transcription and NER. In transcription, TFIIH is a component of the pre-initiation complex (PIC) and is important for promoter opening and the phosphorylation of RNA Polymerase II (RNA Pol II). During repair, TFIIH is important for DNA unwinding, recruitment of downstream repair factors, and verification of the bulky lesion. Several different disease states can arise from mutations within subunits of the TFIIH complex. Most strikingly are Xeroderma Pigmentosum (XP), XP combined with Cockayne Syndrome (CS), and Trichothiodystrophy (TTD). Here, we summarize the recruitment and functions of TFIIH in the two NER subpathways, global genomic (GG-NER) and transcription-coupled NER (TC-NER). We will also discuss how TFIIH’s roles in the two subpathways lead to different genetic disorders.
15 Apr 2023Submitted to Environmental and Molecular Mutagenesis
17 Apr 2023Submission Checks Completed
17 Apr 2023Assigned to Editor
17 Apr 2023Review(s) Completed, Editorial Evaluation Pending
21 Apr 2023Reviewer(s) Assigned
22 May 2023Editorial Decision: Revise Minor
05 Jul 20231st Revision Received
07 Jul 2023Submission Checks Completed
07 Jul 2023Assigned to Editor
07 Jul 2023Review(s) Completed, Editorial Evaluation Pending
15 Jul 2023Reviewer(s) Assigned
03 Aug 2023Editorial Decision: Accept