Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response

Idit Hazan, Thomas G. Hofmann, Rami I. Aqeilan*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations

Abstract

The role of common fragile sites (CFSs) in cancer remains controversial. Two main views dominate the discussion: one suggests that CFS loci are hotspots of genomic instability leading to inactivation of genes encoded within them, while the other view proposes that CFSs are functional units and that loss of the encoded genes confers selective pressure, leading to cancer development. The latter view is supported by emerging evidence showing that expression of a given CFS is associated with genome integrity and that inactivation of CFS-resident tumor suppressor genes leads to dysregulation of the DNA damage response (DDR) and increased genomic instability. These two viewpoints of CFS function are not mutually exclusive but rather coexist; when breaks at CFSs are not repaired accurately, this can lead to deletions by which cells acquire growth advantage because of loss of tumor suppressor activities. Here, we review recent advances linking some CFS gene products with the DDR, genomic instability, and carcinogenesis and discuss how their inactivation might represent a selective advantage for cancer cells.

Original languageAmerican English
Article numbere1006436
JournalPLoS Genetics
Volume12
Issue number12
DOIs
StatePublished - Dec 2016

Bibliographical note

Publisher Copyright:
© 2016 Hazan et al.

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