TY - JOUR

T1 - Transcription-Coupled Nucleotide Excision Repair and the Transcriptional Response to UV-Induced DNA Damage

AU - Nieto Moreno, Nicolás

AU - Olthof, Anouk M.

AU - Svejstrup, Jesper Q.

N1 - Publisher Copyright: Copyright © 2023 by the author(s).

PY - 2023

Y1 - 2023

N2 - Ultraviolet (UV) irradiation and other genotoxic stresses induce bulky DNA lesions, which threaten genome stability and cell viability. Cells have evolved two main repair pathways to remove such lesions: global genome nucleotide excision repair (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER). The modes by which these subpathways recognize DNA lesions are distinct, but they converge onto the same downstream steps for DNA repair. Here, we first summarize the current understanding of these repair mechanisms, specifically focusing on the roles of stalled RNA polymerase II, Cockayne syndrome protein B (CSB), CSA and UV-stimulated scaffold protein A (UVSSA) in TC-NER. We also discuss the intriguing role of protein ubiquitylation in this process. Additionally, we highlight key aspects of the effect of UV irradiation on transcription and describe the role of signaling cascades in orchestrating this response. Finally, we describe the pathogenic mechanisms underlying xeroderma pigmentosum and Cockayne syndrome, the two main diseases linked to mutations in NER factors.

AB - Ultraviolet (UV) irradiation and other genotoxic stresses induce bulky DNA lesions, which threaten genome stability and cell viability. Cells have evolved two main repair pathways to remove such lesions: global genome nucleotide excision repair (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER). The modes by which these subpathways recognize DNA lesions are distinct, but they converge onto the same downstream steps for DNA repair. Here, we first summarize the current understanding of these repair mechanisms, specifically focusing on the roles of stalled RNA polymerase II, Cockayne syndrome protein B (CSB), CSA and UV-stimulated scaffold protein A (UVSSA) in TC-NER. We also discuss the intriguing role of protein ubiquitylation in this process. Additionally, we highlight key aspects of the effect of UV irradiation on transcription and describe the role of signaling cascades in orchestrating this response. Finally, we describe the pathogenic mechanisms underlying xeroderma pigmentosum and Cockayne syndrome, the two main diseases linked to mutations in NER factors.

KW - Cockayne syndrome

KW - DNA repair

KW - global genome nucleotide excision repair

KW - RNA polymerase II

KW - transcription

KW - transcription-coupled nucleotide excision repair

U2 - 10.1146/annurev-biochem-052621-091205

DO - 10.1146/annurev-biochem-052621-091205

M3 - Review

C2 - 37040775

AN - SCOPUS:85163920851

VL - 92

SP - 81

EP - 113

JO - Annual Review of Biochemistry

JF - Annual Review of Biochemistry

SN - 0066-4154

ER -