Fragile X Explained — Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in males. It is caused by an abnormally high number of copies of CGG trinucleotides in the X chromosome’s Fragile X Mental Retardation (FMR1)gene (frequently more than 200 copies vs. 5 to 54 copies in unaffected versions of FMR1). These extra CGG copies mean that the FMR1 gene can’t code for the important neural development protein FMRP, resulting in the signs and symptoms of FXS. Drs. Carl Schildkraut and Jeannine Gerhardt compared the DNA replication of the FMR1 gene in normal and FXS human embryonic stem cells (hESCs). They looked specifically in which direction the replication fork, the Y-shaped structure formed when the double-stranded DNA molecule unwinds so that both single strands can serve as templates for DNA replication, proceeds through the FMR1 gene. The researchers observed that the FXS hESCs used a different “origin of replication” (a special DNA region responsible for initiating the duplication of nearby DNA), which changed the direction of DNA replication through the FMR1 gene. This change in replication direction may explain the expansion of CGG repeats that results in FXS. The findings were published in the January 9, 2014 issue of Molecular Cell. Dr. Schildkraut is professor of cell biology; Dr. Gerhardt is an associate in the department of cell biology.
Posted on: Thursday, February 13, 2014