Topoisomerase II- and condensin-dependent breakage of MEC1ATR-sensitive fragile sites occurs independently of spindle tension, anaphase, or cytokinesis.

Fragile sites are loci of recurrent chromosome breakage in the genome. They are found in organisms ranging from bacteria to humans and are implicated in genome instability, evolution, and cancer. In budding yeast, inactivation of Mec1, a homolog of mammalian ATR, leads to chromosome breakage at fragile sites referred to as replication slow zones (RSZs).

Regulation of fragile sites expression in budding yeast by MEC1, RRM3 and hydroxyurea.

Fragile sites are specific loci within the genome that exhibit increased tendencies for chromosome breakage. They are conserved among mammals and are also found in lower eukaryotes including yeast and fly. Many conditions, including mutations and exogenous factors, contribute to fragile site expression, but the nature of interaction among them remains elusive.