Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites

  • Wenyi FengEmail author
  • Arijita Chakraborty
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1042)


Chromosome fragile sites are a fascinating cytogenetic phenomenon now widely implicated in a slew of human diseases ranging from neurological disorders to cancer. Yet, the paths leading to these revelations were far from direct, and the number of fragile sites that have been molecularly cloned with known disease-associated genes remains modest. Moreover, as more fragile sites were being discovered, research interests in some of the earliest discovered fragile sites ebbed away, leaving a number of unsolved mysteries in chromosome biology. In this review we attempt to recount some of the early discoveries of fragile sites and highlight those phenomena that have eluded intense scrutiny but remain extremely relevant in our understanding of the mechanisms of chromosome fragility. We then survey the literature for disease association for a comprehensive list of fragile sites. We also review recent studies addressing the underlying cause of chromosome fragility while highlighting some ongoing debates. We report an observed enrichment for R-loop forming sequences in fragile site-associated genes than genomic average. Finally, we will leave the reader with some lingering questions to provoke discussion and inspire further scientific inquiries.


Chromosome fragility Common and rare fragile sites DNA double-strand breaks DNA replication stress R-loops Aphidicolin Folate stress Neurological disorders Cancer 



We thank Andrew McCulley for assisting data analysis during this work. This work was supported by the National Institutes of Health (5R01 GM118799-01A1 to W.F.).


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© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologySUNY Upstate Medical UniversitySyracuseUSA

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