Saccharomyces cerevisiae rDNA as super-hub: the region where replication, transcription and recombination meet

Saccharomyces cerevisiae ribosomal DNA, the repeated region where rRNAs are synthesized by about 150 encoding units, hosts all the protein machineries responsible for the main DNA transactions such as replication, transcription and recombination. This and its repetitive nature make rDNA a unique and complex genetic locus compared to any other. All the different molecular machineries acting in this locus need to be accurately and finely controlled and coordinated and for this reason rDNA is one of the most impressive examples of highly complex molecular regulated loci. The region in which the large molecular complexes involved in rDNA activity and/or regulation are recruited is extremely small: that is, the 2.5 kb long intergenic spacer, interrupting each 35S RNA coding unit from the next. All S. cerevisiae RNA polymerases (I, II and III) transcribing the different genetic rDNA elements are recruited here; a sequence responsible for each rDNA unit replication, which needs its molecular apparatus, also localizes here; moreover, it is noteworthy that the rDNA replication proceeds almost unidirectionally because each replication fork is stopped in the so-called replication fork barrier. These localized fork blocking events induce, with a given frequency, the homologous recombination process by which cells maintain a high identity among the rDNA repeated units. Here, we describe the different processes involving the rDNA locus, how they influence each other and how these mutual interferences are highly regulated and coordinated. We propose that an rDNA conformation as a super-hub could help in optimizing the micro-environment for all basic DNA transactions.