Genome instability: a mechanistic view of its causes and consequences.

Genomic instability in the form of mutations and chromosome rearrangements is usually associated with pathological disorders, and yet it is also crucial for evolution. Two types of elements have a key role in instability leading to rearrangements: those that act in trans to prevent instability--among them are replication, repair and S-phase checkpoint factors--and those that act in cis--chromosomal hotspots of instability such as fragile sites and highly transcribed DNA sequences. Taking these elements as a guide, we review the causes and consequences of instability with the aim of providing a mechanistic perspective on the origin of genomic instability.