Recent Advancements in DNA Damage–Transcription Crosstalk and High-Resolution Mapping of DNA Breaks

Abstract

Until recently, DNA damage arising from physiological DNA metabolism was considered a detrimental by-product for cells. However, an increasing amount of evidence has shown that DNA damage could have a positive role in transcription activation. In particular, DNA damage has been detected in transcriptional elements following different stimuli. These physiological DNA breaks are thought to be instrumental for the correct expression of genomic loci through different mechanisms. In this regard, although a plethora of methods are available to precisely map transcribed regions and transcription start sites, commonly used techniques for mapping DNA breaks lack sufficient resolution and sensitivity to draw a robust correlation between DNA damage generation and transcription. Recently, however, several methods have been developed to map DNA damage at single-nucleotide resolution, thus providing a new set of tools to correlate DNA damage and transcription. Here, we review how DNA damage can positively regulate transcription initiation, the current techniques for mapping DNA breaks at high resolution, and how these techniques can benefit future studies of DNA damage and transcription.

Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks

“…These events are reminiscent of those at the centromeric locus in Schizosaccharomyces pombe , where small RNAs generated by Dicer bind to a nascent transcript that is also their precursor and together maintain the epigenetic and genetic stability of the locus 41 . The proposed model fits with the growing list of small ncRNAs interacting with and regulating long ncRNAs 42 and, more in general, with the emerging interplay between DSB and transcriptional control 43 .…”

High Throughput Screening for Natural Host Defense Peptide-Inducing Compounds as Novel Alternatives to Antibiotics

“…Therefore, it is very likely these quercetin-like flavonoids have histone modifying functions as well. Besides histone acetylation, four compounds including sanguinarine, wortmannin, hypocrellin B, and radicicol are known to induce DNA damage, inhibit DNA repair or DNA topoisomerase II activity (Xu et al, 1998 ; Hashimoto et al, 2003 ; Barker et al, 2006 ; Matkar et al, 2008 ), which has been recently revealed to exert a positive role in initiation of gene transcription (Pommier et al, 2016 ; Vitelli et al, 2017 ). Additionally, radicicol, sclerotiorin, and sanguinarine are capable of inhibiting heat shock protein 90 (HSP90) (Davenport et al, 2014 ; Kabbaj et al, 2015 ; Khandelwal et al, 2016 ), which is known to interact with DNA topoisomerase II (Barker et al, 2006 ) and whose activity is regulated by reversible acetylation (Prodromou, 2016 ).…”

Integrating the DNA damage and protein stress responses during cancer development and treatment

“…If this spatiotemporal process is altered by misregulation of an RT‐related gene or a replication process step, e.g. replication licensing* , the propensity to DSB formation due to replication–transcription collision increases . In this regard, low‐density replication–initiation may lead to unfinished replication, owing to the long distance between replication forks, making breakage a probable event .…”