Stories about: chromosomes

The shape of things in the genome, and how chromosomes break

While a cell's chromosomes (red, in a dividing cell) may look like they sit in a tangled jumble, they are actually organized in precise 3D fashion, which in turn influences what happens when chromosomes break. (Lothar Schmermelleh/Wikimedia Commons)

We’ve known for decades that our chromosomes can break and reshuffle, especially in cancer cells. We also see this process, called translocation, in naïve B cells when they start to produce antibodies for the first time: the cell breaks, shuffles and recombines genes to decide which threat it will defend against.

But knowing these things happen doesn’t mean that we’ve understood the rules for how and why they happen. By combining two powerful methods of genomic mapping, a research team led by Frederick Alt, director of the Program in Cellular and Molecular (PCMM) Medicine at Children’s Hospital Boston and the Immune Disease Institute (IDI), has brought some of those rules into clearer focus. It turns out that the genome’s three-dimensional organization – where each of the genome’s thousands of genes lie spatially within the cell’s nucleus – holds great influence over where broken chromosome ends rejoin.

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Cancer genetics: Learning the rules for breaking chromosomes

The chromosomes of cancer cells aren’t laid out nearly this neatly. Parts of them get broken off and reshuffled, but there are some rules for where those breaks occur, rules that Fred Alt wants to understand. (NHGRI)

In many cancers chromosomes get reshuffled, with sections breaking off and attaching to other chromosomes in what are called translocations. Fred Alt and his team are trying to better understand where chromosomes are most likely to break and where the broken pieces are most likely to attach, knowledge that could help better understand some aspects of cancer. Think of it as another set of rules layered on top of the rules (e.g., as which genes to turn on, which to turn off, and when) that govern how the genome works.

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