Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 1997 Apr 29;94(9):4587-92.
doi: 10.1073/pnas.94.9.4587.

A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication

R S Hansen  1 , T K Canfield, A D Fjeld, S Mumm, C D Laird, S M Gartler
Affiliations
Comparative Study

A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication

R S Hansen et al. Proc Natl Acad Sci U S A. .

Abstract

The timing of DNA replication in the Xq27 portion of the human X chromosome was studied in cells derived from normal and fragile X males to further characterize the replication delay on fragile X chromosomes. By examining a number of sequence-tagged sites (STSs) that span several megabases of Xq27, we found this portion of the normal active X chromosome to be composed of two large zones with different replication times in fibroblasts, lymphocytes, and lymphoblastoid cells. The centromere-proximal zone replicates very late in S, whereas the distal zone normally replicates somewhat earlier and contains FMR1, the gene responsible for fragile X syndrome when mutated. Our analysis of the region of delayed replication in fragile X cells indicates that it extends at least 400 kb 5' of FMR1 and appears to merge with the normal zone of very late replication in proximal Xq27. The distal border of delayed replication varies among different fragile X males, thereby defining three replicon-sized domains that can be affected in fragile X syndrome. The distal boundary of the largest region of delayed replication is located between 350 and 600 kb 3' of FMR1. This example of variable spreading of late replication into multiple replicons in fragile X provides a model for the spread of inactivation associated with position-effect variegation or X chromosome inactivation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Physical map of the late-replicating G band, Xq27. STSs used for replication timing were placed according to contig mapping data (ref. and S.M., unpublished observations).
Figure 2
Figure 2
Replication timing within Xq27 in normal and fragile X males. Replication patterns of several STSs within Xq27 are shown for a normal male lymphoblastoid cell line (FF) and two fragile X lymphoblasts (H6 and TL009). (A) Membrane hybridization signals are derived from BrdUrd incorporation into the analyzed locus at different portions of the cell cycle that correspond to flow cytometry fractions G1, four fractions of S (S1, S2, S3, and S4), and G2/M. Arrows designate regions that have a strong delay in replication. (B) Other examples of variability in the distal border of delayed replication in fragile X lymphoblasts.
Figure 3
Figure 3
Delayed replication is present in untransformed cells derived from fragile X patients. Replication patterns of Xq27 STSs are shown for fibroblasts (A) and mitogen-stimulated peripheral lymphocytes (B) that were derived from normal and fragile X males to examine further the delayed replication domain on fragile X chromosomes. Delayed replication was observed in all the fragile X cultures (arrows indicate strong replication delay).
Figure 4
Figure 4
Summary of fragile X-associated regions of delayed replication. A map of Xq27 replication time zones on the active X chromosome is shown for normal and fragile X cells to illustrate regions of marked replication delay found in different fragile X cell lines or cell cultures.
See this image and copyright information in PMC

References

    1. Hansen R S, Canfield T K, Lamb M M, Gartler S M, Laird C D. Cell. 1993;73:1403–1409. - PubMed
    1. Hansen R S, Canfield T K, Gartler S M. Hum Mol Genet. 1995;4:813–820. - PubMed
    1. Drouin R, Holmquist G P, Richer C-L. Adv Hum Genet. 1994;22:47–115. - PubMed
    1. Goldman M A, Holmquist G P, Gray M C, Caston L A, Nag A. Science. 1984;224:686–692. - PubMed
    1. Hatton K S, Dhar V, Brown E H, Iqbal M A, Stuart S, Didamo V T, Schildkraut C L. Mol Cell Biol. 1988;8:2149–2158. - PMC - PubMed

Publication types