7AD8

Core TFIIH-XPA-DNA complex with modelled p62 subunit

7AD8 の概要

• エントリーDOI: 10.2210/pdb7ad8/pdb
• 関連するPDBエントリー: 6RO4
• EMDBエントリー: 4970
• 分子名称: DNA (49-MER), General transcription factor IIH subunit 1, IRON/SULFUR CLUSTER, ... (12 entities in total)
• 機能のキーワード: dna repair, transcription factor, dna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 440024.33

構造登録者

Koelmel, W.,Kuper, J.,Kisker, C. (登録日: 2020-09-14, 公開日: 2021-07-28, 最終更新日: 2024-05-15)

主引用文献

Barnett, J.T.,Kuper, J.,Koelmel, W.,Kisker, C.,Kad, N.M.
The TFIIH subunits p44/p62 act as a damage sensor during nucleotide excision repair.
Nucleic Acids Res., 48:12689-12696, 2020

PubMed Abstract: Nucleotide excision repair (NER) in eukaryotes is orchestrated by the core form of the general transcription factor TFIIH, containing the helicases XPB, XPD and five 'structural' subunits, p62, p44, p34, p52 and p8. Recent cryo-EM structures show that p62 makes extensive contacts with p44 and in part occupies XPD's DNA binding site. While p44 is known to regulate the helicase activity of XPD during NER, p62 is thought to be purely structural. Here, using helicase and adenosine triphosphatase assays we show that a complex containing p44 and p62 enhances XPD's affinity for dsDNA 3-fold over p44 alone. Remarkably, the relative affinity is further increased to 60-fold by dsDNA damage. Direct binding studies show this preference derives from p44/p62's high affinity (20 nM) for damaged ssDNA. Single molecule imaging of p44/p62 complexes without XPD reveals they bind to and randomly diffuse on DNA, however, in the presence of UV-induced DNA lesions these complexes stall. Combined with the analysis of a recent cryo-EM structure, we suggest that p44/p62 acts as a novel DNA-binding entity that enhances damage recognition in TFIIH. This revises our understanding of TFIIH and prompts investigation into the core subunits for an active role during DNA repair and/or transcription.

PubMed: 33166411
DOI: 10.1093/nar/gkaa973

実験手法

ELECTRON MICROSCOPY (3.5 Å)