Scientists discover the enzyme that lets cancer rapidly rewire its DNA

 


Chromothripsis is also surprisingly common. Studies suggest that about one in four cancers shows signs of this type of chromosome damage, and in some cancers the rate is even higher. Nearly all osteosarcomas, an aggressive bone cancer, display evidence of chromothripsis, and many brain cancers show especially elevated levels.

"This discovery finally reveals the molecular 'spark' that ignites one of the most aggressive forms of genome rearrangement in cancer," said senior author Don Cleveland, Ph.D., professor of cellular and molecular medicine at UC San Diego School of Medicine and member of UC San Diego Moores Cancer Center. "By finding what breaks the chromosome in the first place, we now have a new and actionable point of intervention for slowing cancer evolution."

Chromothripsis begins when errors during cell division trap individual chromosomes inside small, fragile compartments known as micronuclei. When a micronucleus ruptures, the chromosome inside is left exposed. At that point, it becomes vulnerable to nucleases, enzymes that can cut DNA strands.

Until now, researchers did not know which nuclease was responsible for triggering this destructive chain reaction, making it impossible to design therapies aimed at stopping it.

To pinpoint the culprit, the team used an imaging based screening approach to systematically examine all known and predicted human nucleases. They monitored how each enzyme behaved in living cancer cells. One enzyme, N4BP2, stood out. It was uniquely able to enter micronuclei and fragment the DNA inside.


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#Cancer #Enzyme #DNA #Mutation #Genomics #Oncology #Biology #Research #Science #Medicine #Tumor #Therapy #Resistance #Discovery #Cellular #Molecular #Innovation #Breakthrough #Health #Precision

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