DNA Housekeeping Proteins May Also Prevent Cancer

Featured Article Academic Journal Main Category: Cancer / Oncology Also Included In: Genetics Article Date: 06 May 2013 - 3:00 PDT

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Senior author Gerald Crabtree, who is also of the Howard Hughes Medical Institute in Chevy Chase, Maryland, and colleagues, write about their findings in a paper published online in Nature Genetics on 5 May.

"Somehow these chromatin-regulatory complexes manage to compress nearly two yards of DNA into a nucleus about one one-thousandth the size of a pinhead. And they do this without compromising the ability of the DNA to be replicated and selectively expressed in different tissues - all without tangling."

More recently, in the journal Nature, they reported that switching subunits in the BAF complexes can transform human fibroblasts to neurons, suggesting they also play an instructive role in cell development, and possibly, cancer.

In this latest study, they show that BAF complexes "are mutated in nearly 20 percent of all human malignancies thus far examined," says Crabtree.

The results also show that the mutations have a broad reach, comparable to that of another well-known tumor suppressor, p53.

"Although we knew that this complex was likely to play a role in preventing cancer, we didn't realize how extensive it would be," says co-first author and postdoctoral scholar Cigall Kadoch.

The team discovered that certain patterns of mutations in the subunits of the BAF complexes seem to precede specific cancers. For example, one pattern suggests ovarian rather than colon cancer will follow.

When they found that in some cases even just one mutation in a subunit was enough to trigger cancer, they realized how important a role BAF complexes must play in tumor suppression.

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DNA Housekeeping Proteins May Also Prevent Cancer