In a mini-review by Ellen Tsang and Anthony Carr, recombination is highly regulated in the rDNA. Repetitive sequences such as rDNA provide good substrates for homologous recombination, particualrly if replication forks collapse here. Several studies have shown that replication fork barrier (RFB)-dependent and -independent replication fork arrest, as well as replication-independent DNA metabolism, can induce recombination in the rDNA. Some of the molecules involved in regulating recombination include Fob1, Sir2, topoisomerase, RNA polymerase I, and HOT1.
They concluded by stating:
“… high levels of rDNA recombination acts to maintain sequence uniformity … it should be noted that the outcomes of recombination within the rDNA are very different to those of recombination at other repeat units within the genome … the specialised nature of the rDNA metabolism suggests that observations made at the rDNA locus may not always be applicable to the wider genome … fork arrest at a replication barrier only generates the potential for recombination; whether recombination occurs or not, and through which pathways, remains the responsibility of other local factors, such as the binding of regulatory protein complexes and sister chromatid cohesion …”
Tsang E, Carr AM.
Replication fork arrest, recombination and the maintenance of ribosomal DNA stability.
DNA Repair (Amst). 2008 Oct 1;7(10):1613-23. Epub 2008 Jul 29.
Fig. 2. Model for the regulation of recombination outcomes in the rDNA. Heavy arrows represent individual rDNA units; those shown in blue are equivalent units on sister chromatids. The open circle denotes an active rARS; the red bar denotes an active RFB. Leftward-moving replication forks arrest at the RFB. A subset is thought to collapse, requiring recombination to restart replication. Under normal circumstances, sister chromatids are held together by cohesin (grey rings), forcing the broken end to invade the equivalent unit to give equal sister chromatid exchange and rDNA stability (A). In cases where cohesin is dissociated from the rDNA, the broken end can invade either an upstream (B) or downstream (C) unit, leading to expansion or contraction of the rDNA array, respectively [17].
PDF (469 K)[17] T. Kobayashi, T. Horiuchi, P. Tongaonkar, L. Vu and M. Nomura, SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast, Cell 117 (2004), pp. 441–453.
DRUSE 