Double strand breaks behind mutation clusters??

Suikerbuik

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I can add this to some topic elsewhere, but I think might be worth its own thread, if not merge these please. Anyway I saw this study a few days back.

However, recent studies have shown that cancer development frequently involves the formation of multiple mutations that arise simultaneously and in close proximity to each other. These groups of clustered mutations are frequently found in regions where chromosomal rearrangements take place.

The formation of clustered mutations may result from the process of DNA repair. Anna Malkova, associate professor of biology in the UI College of Liberal Arts and Sciences, notes that the DNA repair pathway, known as break-induced replication (BIR), can promote clusters of DNA mutations.

"Previously, we have shown that double-strand DNA breaks, which can result from oxidation, ionizing radiation and replication errors, can be repaired by BIR," says Malkova.

Estrogen is another one that is capable to induce double-strand breaks. So maybe all xeno-estrogens, if they agonize the ERa receptor, have the ability to induce mutations.

http://carcin.oxfordjournals.org/content/32/3/279.full.pdf

In the Cell Reports study, researchers subjected yeast cells undergoing BIR to alkylating (cancer cell-killing agents) damage. "We found that the single-stranded DNA regions that accumulate during BIR are susceptible to damage that leads to the formation of mutation clusters," explains Cynthia Sakofsky, postdoctoral fellow at the UI and one of two co-first authors on the paper. "These clusters are similar to those found in human cancer," she says.

Importantly, say the researchers, the paper provides a mechanism to potentially explain how genetic changes form in human cancers. Thus, it will be critical for future research to determine whether BIR can form clustered mutations that lead to cancer in humans. If this turns out to be true, it may lead to the discovery of new targets for developing therapies against human cancers.

http://www.sciencedaily.com/releases/2014/07/140730173130.htm
 
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