Genome instability: a mechanistic view of its causes and consequences

Nat Rev Genet. 2008 Mar;9(3):204-17. doi: 10.1038/nrg2268.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Breaks
  • DNA Replication
  • Evolution, Molecular
  • Genomic Instability*
  • Humans
  • Immunoglobulin Class Switching