Fragile sites

Definition

Fragile sites are chromosomal regions that are susceptible to gaps or breaks. Common fragile sites occur in all individuals, are thought to be sensitive to replication stress due to chromosome structure, and are often re-arranged in cancer. Rare fragile sites are caused by nucleotide repeats and are inherited.

Latest Research and Reviews

  • Reviews |

    This Opinion article discusses recent studies that have provided new insights into the mechanisms of common fragile site instability and the resulting genomic effects, which include the generation of focal copy number alterations that affect the genomic landscape of many cancers.

    • Thomas W. Glover
    • , Thomas E. Wilson
    •  & Martin F. Arlt
    Nature Reviews Cancer 17, 489–501
  • Research | | open

    The budding yeast genome encodes two Pif1 family helicases, Pif1 and Rrm3, previously shown to have distinct functions in the maintenance of telomeres and other aspects of genome stability. Here the authors identify a role for Pif1 (and Rrm3) in promoting DNA replication and suppressing R-loop mediated DNA damage at tRNA genes.

    • Phong Lan Thao Tran
    • , Thomas J. Pohl
    • , Chi-Fu Chen
    • , Angela Chan
    • , Sebastian Pott
    •  & Virginia A. Zakian
  • Research | | open

    Translesion synthesis polymerase eta has a well characterized role in replicating past UV-induced DNA lesions and has recently been shown to act at difficult to replicate sequences. Here the authors show that its SUMOylation is required to recruit pol eta at the replication fork and to prevent under-replicated DNA.

    • Emmanuelle Despras
    • , Méghane Sittewelle
    • , Caroline Pouvelle
    • , Noémie Delrieu
    • , Agnès M Cordonnier
    •  & Patricia L Kannouche
  • Research |

    Common fragile sites (CFSs) are difficult-to-replicate regions of eukaryotic genomes that are sensitive to replication stress and that require resolution by the MUS81–EME1 endonuclease to re-initiate POLD3-dependent DNA synthesis in early mitosis; this study defines the specific pathway of events causing the CFS fragility phenotype.

    • Sheroy Minocherhomji
    • , Songmin Ying
    • , Victoria A. Bjerregaard
    • , Sara Bursomanno
    • , Aiste Aleliunaite
    • , Wei Wu
    • , Hocine W. Mankouri
    • , Huahao Shen
    • , Ying Liu
    •  & Ian D. Hickson
    Nature 528, 286–290
  • Research |

    Aberrant oncogene expression can cause replication stress leading to chromosomal breaks. Here the authors map the chromosomal break loci induced by two different oncogenes and by a replication inhibitor, and show that each treatment induces a unique pattern of breaks in the same cell type.

    • Karin Miron
    • , Tamar Golan-Lev
    • , Raz Dvir
    • , Eyal Ben-David
    •  & Batsheva Kerem

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