Albany 2013: Book of Abstracts

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Conversation 18
June 11-15 2013
©Adenine Press (2012)

The Molecular Mechanism of Breakage at Fragile Site FRA16D

Replication stress induces physical breakage at discrete loci in chromosomes, which can be visualized on a metaphase chromosome spread. These common fragile sites (CFS) are conserved across species and are hotspots for sister chromatid recombination, viral integration, rearrangements, translocations, and deletions (Glover et al 2005). Despite multiple theories, the molecular mechanisms of CFS expression and genomic instability are still not well understood. The fragile site FRA16D is of special interest because it is the second most highly expressed fragile site and is located within the WWOX tumor suppressor gene. Previous data identified a polymorphic AT repeat within a FRA16D subregion called F1 that causes chromosome fragility and replication fork stalling in a yeast model (Zhang and Freudenreich 2007). Recently, we have found that breakage increases in an AT repeat length-dependent manner. Our results suggest that the AT repeat in the context of F1 forms a secondary structure, making the region more vulnerable to breakage.

This research has been supported by the Tufts University Biology Department and the Tufts University Dean’s Fund.


    T.W. Glover, M.F.A. & Casper, A. (2005) Mechanisms of common fragile site instability. Hum. Mol. Gen. Spec No. 2, R197-205.

    H. Zhang & Freudenreich, C.H. (2007) An AT-Rich Sequence in Human Common Fragile Site FRA16D Causes Fork Stalling and Chromosome Breakage in S. cerevisiae. Mol. Cell. Biol. 27, 367-79.

Simran Kaushal
Soo-Mi Alison Lee
Nealia House
Keerthana Gnanapradeepan
Adam Snider
Xiaofeng Allen Su
Catherine H. Freudenreich

200 Boston Ave Suite 4700
Department of Biology
Tufts University
Medford, MA 02155

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