Genome Instability of Repetitive Sequence: Lesson from the Ribosomal RNA Gene Repeat

Abstract

Chromosomal DNA is not equally stable all over the genome. Some regions, especially those characterized by repetitive sequences, are known to be “fragile sites” where DNA damage occurs more frequently than in other regions. In such regions, DNA replication is inhibited and DNA double-strand breaks are induced. Repetitive sequences easily form DNA secondary structures, and during repair of double-strand breaks, a broken end may recombine with a repeat at the non-original site which results in translocation. The well-studied ribosomal RNA gene repeat (called rDNA) is the largest repetitive region in the eukaryotic genome. In the case of budding yeast, the rDNA occupies ~10 % of the genome. Because of the size and unstable features of rDNA, its stability dominates that of the overall genome and affects cellular functions, such as senescence. In this review, I will introduce the unique mechanisms by which the rDNA repetitive region and its physiological functions are maintained.