R/G-band boundaries: genomic instability and human disease

The human genome is composed of large-scale compartmentalized structures resulting from variations in the amount of guanine and cytosine residues (GC%) and in the timing of DNA replication. These compartmentalized structures are related to the light- and dark-staining bands along chromosomes after the appropriate staining. Here we describe our current understanding of the biological importance of the boundaries between these light and dark bands (the so-called R/G boundaries). These R/G boundaries were identified following integration of information obtained from analyses of chromosome bands and genome sequences. This review also discusses the potential medical significance of these chromosomal regions for conditions related to genomic instability, such as cancer and neural disease. We propose that R/G-chromosomal boundaries, which correspond to regions showing a switch in replication timing from early to late S phase (early/late-switch regions) and of transition in GC%, have an extremely low number of replication origins and more non-B-form DNA structures than other genomic regions. Further, we suggest that genes located at R/G boundaries and which contain such DNA sequences have an increased risk of genetic instability and of being associated with human diseases. Finally, we propose strategies for genome and epigenome analyses based on R/G boundaries.