The genes encoding ribosomal RNA (rRNA) are the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome. A unique gene amplification system compensates for loss of copies, thus maintaining copy number, albeit with some fluctuations. The unusual nature of rRNA gene repeats affects cellular functions such as senescence. In addition, we recently found that the repeat number determines sensitivity to DNA damage. In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.