Unfaithful Encounters

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Science  22 Jan 2010:
Vol. 327, Issue 5964, pp. 394
DOI: 10.1126/science.327.5964.394-c

Chromosomal translocations, whereby nonadjacent regions of chromosomes are inappropriately joined, are a hallmark of several different types of cancer. They can result in the generation of fusion proteins that bypass normal control mechanisms and can wreak havoc in cells. It has been assumed that translocation events occur randomly; whether more ordered processes are involved has been unclear.

The androgen receptor is a transcription factor that regulates gene expression during prostate development. Fusions between an androgen receptor target gene and genes encoding members of the ETS family of transcription factors place ETS proteins under the control of androgen and are associated with prostate cancer. Using androgen-responsive prostate cells, Lin et al. could produce cancer-specific gene fusions by inducing genotoxic stress and adding androgen. The activation of the androgen receptor promoted encounters between physically separate genes in the nuclei of prostate cells, and genotoxic stress induced double-stranded breaks in intronic regions of these genes. Furthermore, androgen and genotoxic stress recruited proteins involved in sensing DNA breaks and mediating chromosomal rearrangements.

Cell 139, 1069 (2009).

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