Molecular basis for damage recognition and verification by XPC-RAD23B and TFIIH in nucleotide excision repair

Hong Mu, Nicholas Geacintov, Suse Broyde, Jung Eun Yeo, Orlando D. Schärer

Research output: Contribution to journalArticle

Abstract

Global genome nucleotide excision repair (GG-NER) is the main pathway for the removal of bulky lesions from DNA and is characterized by an extraordinarily wide substrate specificity. Remarkably, the efficiency of lesion removal varies dramatically and certain lesions escape repair altogether and are therefore associated with high levels of mutagenicity. Central to the multistep mechanism of damage recognition in NER is the sensing of lesion-induced thermodynamic and structural alterations of DNA by the XPC-RAD23B protein and the verification of the damage by the transcription/repair factor TFIIH. Additional factors contribute to the process: UV-DDB, for the recognition of certain UV-induced lesions in particular in the context of chromatin, while the XPA protein is believed to have a role in damage verification and NER complex assembly. Here we consider the molecular mechanisms that determine repair efficiency in GG-NER based on recent structural, computational, biochemical, cellular and single molecule studies of XPC-RAD23B and its yeast ortholog Rad4. We discuss how the actions of XPC-RAD23B are integrated with those of other NER proteins and, based on recent high-resolution structures of TFIIH, present a structural model of how XPC-RAD23B and TFIIH cooperate in damage recognition and verification.

Original languageEnglish (US)
JournalDNA Repair
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

DNA Repair
Repair
Nucleotides
Transcription Factor TFIIH
Genome
Proteins
Structural Models
DNA
Substrate Specificity
Thermodynamics
Genes
Chromatin
Yeasts
Transcription
Yeast
Molecules
Substrates
DDB

Keywords

  • DNA damage recognition
  • Molecular dynamics simulations
  • Nucleotide excision repair
  • TFIIH
  • UV-DDB
  • XPC-RAD23B

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Molecular basis for damage recognition and verification by XPC-RAD23B and TFIIH in nucleotide excision repair. / Mu, Hong; Geacintov, Nicholas; Broyde, Suse; Yeo, Jung Eun; Schärer, Orlando D.

In: DNA Repair, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Schärer, Orlando D.

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