The genome is a highly organized and compartmentalized structure, which undergoes many dynamic events over the course of a cell cycle, including DNA replication. Standard microscopy techniques have enabled the visualization of replication sites, but with a diffraction-limited resolution of ~250 nm. Yet, the smallest units of chromatin are rather in the scale of a few nanometers. Although informative, standard microscopy images of the genome are only a blurred rendering of the actual biological structure. The emergence of super-resolution techniques in recent years has opened new avenue for the visualization of genomic events. In this note, we describe how single-molecule localization microscopy (SMLM) can be a powerful tool to study DNA replication sites.

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