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

Abstract

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.