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Review
. 2022 May 25;54(6):807-819.
doi: 10.3724/abbs.2022054.

Nucleotide excision repair: a versatile and smart toolkit

Xiping Zhang, Mengdie Yin, Jinchuan Hu
Review

Nucleotide excision repair: a versatile and smart toolkit

Xiping Zhang et al. Acta Biochim Biophys Sin (Shanghai). .

Abstract

Nucleotide excision repair (NER) is a major pathway to deal with bulky adducts induced by various environmental toxins in all cellular organisms. The two sub-pathways of NER, global genome repair (GGR) and transcription-coupled repair (TCR), differ in the damage recognition modes. In this review, we describe the molecular mechanism of NER in mammalian cells, especially the details of damage recognition steps in both sub-pathways. We also introduce new sequencing methods for genome-wide mapping of NER, as well as recent advances about NER in chromatin by these methods. Finally, the roles of NER factors in repairing oxidative damages and resolving R-loops are discussed.

Keywords: damage recognition; global genome repair; nucleotide excision repair; repair mapping; transcription-coupled repair.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

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Figure 1
Mechanistic model of nucleotide excision repair In GGR, lesions are first recognized by DDB complex, then XPC, TFIIH, XPA and RPA, XPG, XPF are sequentially recruited while DDB and XPC are released before the dual incisions step. In TCR, blocked Pol II serves as the damage sensor to recruit CSB, CSA and UVSSA, which corporately recruit TFIIH. The details happened between TFIIH loading and dual incisions are unclear. Nonetheless, for both sub-pathways, XPG and XPF make the 3′ and 5′ incisions, respectively, to generate ~26 nt-long ssDNA fragments containing damage which are released in complex with TFIIH and XPG. The resulted gaps are sealed by DNA polymerases and ligases to recover intact dsDNA.
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Figure 2
Nucleotide excision repair in chromatin environment (A) Chromatin factors that may affect NER, including histone modifications, transcription, transcription factor binding, nucleosome positioning and genome accessibility. TF is short for transcription factor. (B) The methodology to map NER across the genome. The indirect strategy measures genomic profiles of damage at different time points and acquires the pattern of accumulated repair during this time course by comparing damage profiles. The direct strategy (XR-seq) maps NER by capturing and sequencing excised oligonucleotides and obtains the snapshot of repair at a specific time point.
See this image and copyright information in PMC

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