Human Molecular Genetics, Vol 8, 431-437, Copyright © 1999 by Oxford University Press
L Wang, J Darling, JS Zhang, H Huang, W Liu and DI Smith
FRA3B at 3p14.2 is the most active of the common fragile sites in the human
genome and is expressed when cells are exposed to the DNA replication
inhibitor, aphidicolin. Several lines of evidence suggest that fragile
sites are regions of late replication. To elucidate the relationship
between the timing of replication across the FRA3B region and its
corresponding fragility, we labeled cells with 5-bromo-2'- deoxyuridine
(BrdU) and adopted an immunofluorescent procedure to visualize late
replicating DNA (BrdU-substituted DNA) in metaphase chromosomes. We also
chose 21 markers along the FRA3B region and analyzed the timing of
replication using BrdU-labeled DNA from different stages of the cell cycle
sorted by flow cytometry. Our results show that there are two distinct
alleles that replicate at different stages in the cell cycle and that
breaks/gaps preferentially occurred on the chromosome 3 with the late
replication allele. These results provide direct evidence that
allele-specific late replication is involved in the fragility of the most
active common fragile site, FRA3B.
ARTICLES
Allele-specific late replication and fragility of the most active common fragile site, FRA3B
Division of Experimental Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic/Foundation, 200 First Street SW, Rochester, MN 55905, USA.
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