Exploring the SSBreakome: genome‐wide mapping of DNA single‐strand breaks by next‐generation sequencing

DNA single‐strand breaks arise from exposure to DNA‐damaging agents and as obligatory intermediates of DNA replication, recombination and repair. Here, we briefly review methods for quantifying these important structures and discuss in detail a series of recently developed approaches for their genome‐wide mapping by next‐generation sequencing. We compare advantages and limitations of these tools and describe how they can provide insight into the impact of single‐strand breaks on the genome. Mapping the genome‐wide distribution of DNA lesions is key to understanding damage signalling and DNA repair in the context of genome and chromatin structure. Analytical tools based on high‐throughput next‐generation sequencing have revolutionized our progress with such investigations, and numerous methods are now available for various base lesions and modifications as well as for DNA double‐strand breaks. Considering that single‐strand breaks are by far the most common type of lesion and arise not only from exposure to exogenous DNA‐damaging agents, but also as obligatory intermediates of DNA replication, recombination and repair, it is surprising that our insight into their genome‐wide patterns, that is the ‘SSBreakome’, has remained rather obscure until recently, due to a lack of suitable mapping technology. Here we briefly review classical methods for analysing single‐strand breaks and discuss and compare in detail a series of recently developed high‐resolution approaches for the genome‐wide mapping of these lesions, their advantages and limitations and how they have already provided valuable insight into the impact of this type of damage on the genome.