Evolution of Common Fragile Sites

Anne Helmrich, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France

Published online: March 2008

DOI: 10.1002/9780470015902.a0020747

Common fragile sites are specific deoxyribonucleic acid (DNA) breakage-prone genomic regions in all healthy humans. Their instability is provoked by replication stress combined with an escape of cell cycle checkpoints. Common fragile sites are favoured regions of chromosomal aberration formation in the neoplastic process. They are inherent parts of the genomes of all so far analysed mammalian species, and recent data support their existence also in yeast. The common fragile site locations are highly conserved between human and other primates as well as between human and mouse. There is no evidence of an involvement of common fragile sites as ‘hotspots’ in chromosome evolution.

Keywords: common fragile sites; chromosome aberrations; replication; evolutionary conservation

Figure 1. Model for instability at common fragile sites. Polymerase motion is slowed down at specific genomic sites giving rise to single-stranded DNA (ssDNA). These ssDNA regions are coated with RPA leading to the activation of the S-phase and/or G2/M checkpoints, in which ATR plays a key role. The appearance of fragile sites on metaphase chromosomes implies that these lesions can occasionally escape checkpoint control. The result is an unreplicated region that, if not properly repaired, can secondarily lead to double-strand breaks (DSBs). Reproduced from Glover TW, Aelt MF, Casper AM and Durkin SG (2005) Mechanisms of common fragile site instability. Human Molecular Genetics 14(Spec No. 2): R197–R205, by permission of Oxford University Press.
Figure 2. FISH mapping of mouse Fra6B1. (a) Aphidicolin-treated mouse metaphase hybridized with two DNA clones that are homologous to human FRA7H. (b) Focused view of the chromosome 6 with the expressed Fra6B1 in 4¢,6-diamidine-2¢-phenylindole dihydrochloride (DAPI) staining (left) and DAPI staining with FISH overlay (right). The chromatin gap (arrow) maps to the region between the red and green clones.
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 Further Reading
    Arlt MF, Durkin SG, Ragland RL and Glover TW (2006) Common fragile sites as targets for chromosome rearrangements. DNA Repair (Amsterdam) 5: 1126–1135.
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Related Sub-Topics:

Evolutionary Genomics | Molecular Evolution | Chromosomes and Chromatin Modifications | DNA Damage and Repair
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Article Title: Evolution of Common Fragile Sites
 
How to Cite close
Helmrich, Anne(Mar 2008) Evolution of Common Fragile Sites. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020747]