2. Academic Validation
  3. Transcription-coupled nucleotide excision repair: New insights revealed by genomic approaches

Transcription-coupled nucleotide excision repair: New insights revealed by genomic approaches

  • DNA Repair (Amst). 2021 Jul;103:103126. doi: 10.1016/j.dnarep.2021.103126.
Mingrui Duan 1,  Rachel M Speer 2,  Jenna Ulibarri 1,  Ke Jian Liu 2,  Peng Mao 3
Affiliations

Affiliations

  • 1 Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, 87131, USA.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, 87131, USA.
  • 3 Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, 87131, USA. Electronic address: [email protected].
PMID: 33894524 DOI: 10.1016/j.dnarep.2021.103126
Abstract

Elongation of RNA polymerase II (Pol II) is affected by many factors including DNA damage. Bulky damage, such as lesions caused by ultraviolet (UV) radiation, arrests Pol II and inhibits gene transcription, and may lead to genome instability and cell death. Cells activate transcription-coupled nucleotide excision repair (TC-NER) to remove Pol II-impeding damage and allow transcription resumption. TC-NER initiation in humans is mediated by Cockayne syndrome group B (CSB) protein, which binds to the stalled Pol II and promotes assembly of the repair machinery. Given the complex nature of the TC-NER pathway and its unique function at the interface between transcription and repair, new approaches are required to gain in-depth understanding of the mechanism. Advances in genomic approaches provide an important opportunity to investigate how TC-NER is initiated upon damage-induced Pol II stalling and what factors are involved in this process. In this Review, we discuss new mechanisms of TC-NER revealed by genome-wide DNA damage mapping and new TC-NER factors identified by high-throughput screening. As TC-NER conducts strand-specific repair of mutagenic damage, we also discuss how this repair pathway causes mutational strand asymmetry in the Cancer genome.

Keywords

CPD-seq; CSB; DNA damage; Mutagenesis; RNA Pol II.

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