A journey through the microscopic ages of DNA replication

Abstract

Scientific discoveries and technological advancements are inseparable but not always take place in a coherent chronological manner. In the next, we will provide a seemingly unconnected and serendipitous series of scientific facts that, in the whole, converged to unveil DNA and its duplication. We will not cover here the many and fundamental contributions from microbial genetics and in vitro biochemistry. Rather, in this journey, we will emphasize the interplay between microscopy development culminating on super resolution fluorescence microscopy (i.e., nanoscopy) and digital image analysis and its impact on our understanding of DNA duplication. We will interlace the journey with landmark concepts and experiments that have brought the cellular DNA replication field to its present state.

Keywords: DNA; DNA replication; Replication foci; Replicon; Replisome; Super resolution microscopy.

Fig. 1

Graphical overview of microscopy developments and their impact on DNA replication studies

Fig. 2

Organization of DNA replication from the genome to the individual replisome/replicon. A fluorescently labeled human HeLa Kyoto cell with a typical late S-phase replication pattern is presented in the top left corner (scale bar = 5 μm). Magnified super-resolution replication foci, with white circles representing individual replication sites displayed in the middle of the top row. A scheme of clustered DNA loops with active replication sites (white) is shown on the right. Starting point of DNA replication, the replication origin (ori), and the region replicated from a single origin displayed in the bottom row. Each replicon is replicated by two replication machineries (magenta), composed of various replication proteins, magnified in the bottom left corner. Adapted from (Chagin et al. ; Chagin et al. 2010)

Fig. 3

Graphical overview of replication foci numbers in correlation with microscopy developments