Genome instability: a mechanistic view of its causes and consequences

14 páginas, 6 figuras, 1 tabla. PMID: 18227811.-- Final full-text version of the paper available at: http://dx.doi.org/10.1038/nrg2268.-- Supplementary material available at: http://www.nature.com/nrg/journal/v9/n3/extref/nrg2268-s1.pdfGenomic 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.Research in A.A.’s laboratory is funded by grants from the Spanish Ministry of Science and Education (BFU2006‑05260), Consolider Ingenio 2010 (CDS2007‑015) and Junta de Andalucía (CVI102 and CVI624).Peer reviewe