Oxidative DNA damage and repair at non-coding regulatory regions

Trends Cell Biol. 2023 Nov;33(11):939-949. doi: 10.1016/j.tcb.2023.03.004. Epub 2023 Apr 6.

Abstract

DNA breaks at protein-coding sequences are well-established threats to tissue homeostasis and maintenance. They arise from the exposure to intracellular and environmental genotoxins, causing damage in one or two strands of the DNA. DNA breaks have been also reported in non-coding regulatory regions such as enhancers and promoters. They arise from essential cellular processes required for gene transcription, cell identity and function. One such process that has attracted recent attention is the oxidative demethylation of DNA and histones, which generates abasic sites and DNA single-strand breaks. Here, we discuss how oxidative DNA breaks at non-coding regulatory regions are generated and the recently reported role of NuMA (nuclear mitotic apparatus) protein in promoting transcription and repair at these regions.

Keywords: DNA repair; NuMA; demethylation; enhancers; promoters; transcription.

Publication types

  • Review