Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Blood. 2006 Jan 15;107(2):777-80. Epub 2005 Sep 29.

A model of oncogenic rearrangements: differences between chromosomal translocation mechanisms and simple double-strand break repair.

Author information

  • 1Department of Medicine and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Abstract

Recurrent reciprocal translocations are present in many hematologic and mesenchymal malignancies. Because significant sequence homology is absent from translocation breakpoint junctions, non-homologous end-joining (NHEJ) pathways of DNA repair are presumed to catalyze their formation. We developed translocation reporters for use in mammalian cells from which NHEJ events can be selected after precise chromosomal breakage. Translocations were efficiently recovered with these reporters using mouse cells, and their breakpoint junctions recapitulated findings from oncogenic translocations. Small deletions and microhomology were present in most junctions; insertions and more complex events also were observed. Thus, our reporters model features of oncogenic rearrangements in human cancer cells. A homologous sequence at a distance from the break site affected the translocation junction without substantially altering translocation frequency. Interestingly, in a direct comparison, the spectrum of translocation breakpoint junctions differed from junctions derived from repair at a single chromosomal break, providing mechanistic insight into translocation formation.

PMID:
16195334
[PubMed - indexed for MEDLINE]
PMCID:
PMC1895622
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1.
Figure 2.
Figure 3.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk