Interplay between genetic and epigenetic factors governs common fragile site instability in cancer

Efrat Ozeri-Galai, Michal Tur-Sinai, Assaf C. Bester, Batsheva Kerem*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

Common fragile sites (CFSs) are regions within the normal chromosomal structure that were characterized as hotspots for genomic instability in cancer almost 30 years ago. In recent years, many efforts have been made to understand the basis of CFS fragility and their involvement in the genomic signature of instability found in malignant tumors. CFSs are among the first regions to undergo genomic instability during cancer development because of their intrinsic sensitivity to replication stress conditions, which result from oncogene expression. The preferred sensitivity of CFSs to replication stress stems from various mechanisms including: replication fork arrest at AT-rich repeats, origin paucity along large genomic regions, failure in activation of dormant origins, late replication timing, collision between replication and transcription along large genes, all leading to incomplete replication of the CFS region and resulting in chromosomal instability. Here we review shared and unique characteristics of CFSs, their underlying causes and implications, particularly for the development of cancer.

Original languageAmerican English
Pages (from-to)4495-4506
Number of pages12
JournalCellular and Molecular Life Sciences
Volume71
Issue number23
DOIs
StatePublished - 9 Oct 2014

Bibliographical note

Publisher Copyright:
© 2014 Springer Basel.

Keywords

  • Cancer
  • DNA damage
  • Dormant origins
  • Fragile sites
  • Genomic instability
  • Replication

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