Barnett, Jamie T., Kuper, J., Koelmel, W., Kisker, C., Kad, Neil M (2019) The TFIIH components p44/p62 act as a damage sensor during nucleotide excision repair. BioRxiv - Preprint Server for Biology, . (Unpublished) (doi:10.1101/643874) (KAR id:74140)
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Official URL https://doi.org/10.1101/643874 |
Abstract
Nucleotide excision repair (NER) protects the genome following exposure to diverse types of DNA damage, including UV light and chemotherapeutics. Mutations in human NER genes lead to diseases such as xeroderma pigmentosum and Cockayne syndrome. In eukaryotes, the major transcription factor TFIIH is the central hub of NER. The core components of TFIIH include the helicases XPB, XPD, and the five core structural subunits. Two of these core-TFIIH proteins, p44 and p62 remain relatively unstudied; although p44 is known to regulate the helicase activity of XPD during NER. p62's role is thought to be structural; however, a recent cryo-EM structure shows p44, p62, and XPD making contacts with each other, implying a more extensive role in DNA repair beyond the structural integrity of TFIIH. Here, we show that p44 stimulates XPD's ATPase, but upon encountering DNA damage further stimulation is only observed when p62 is in the ternary complex. More significantly, we show that the p44/p62 complex binds DNA independently of XPD and diffuses along its backbone, indicating a novel DNA-binding entity in TFIIH. These data support a role for p44/p62 in TFIIH's mechanism of damage detection. This revises our understanding of TFIIH and prompts more extensive investigation of all of the core subunits, for an active role during both DNA repair and transcription.
Item Type: | Article |
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DOI/Identification number: | 10.1101/643874 |
Subjects: | Q Science > QH Natural history > QH301 Biology |
Divisions: | Divisions > Division of Natural Sciences > School of Biosciences |
Depositing User: | Neil Kad |
Date Deposited: | 28 May 2019 10:46 UTC |
Last Modified: | 06 May 2020 03:19 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/74140 (The current URI for this page, for reference purposes) |
Kad, Neil M: | ![]() |
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