RESUMO
Unique repetitive elements of the eukaryotic genome can be problematic for cellular DNA replication and transcription and pose a source of genomic instability. Human ribosomal DNA (rDNA) exists as repeating units clustered together on several chromosomes. Understanding the molecular mechanisms whereby rDNA interferes with normal genome homeostasis is the subject of this review. We discuss the instability of rDNA as a driver of senescence and the important roles of helicases to suppress its deleterious effects. The propensity of rDNA that is rich in guanine bases to form G-quadruplexes (G4) is discussed and evaluated in disease pathogenesis. Targeting G4 in the ribosomes and other chromosomal loci may represent a useful synthetic lethal approach to combating cancer.