Yeast study reveals the benefits of gene amplification

Dec. 3 (UPI) — Thanks to a new study of satellite DNA and its formation in yeast cells, scientists are gaining insight into the benefits and pitfalls of genome amplification.

To ward off environmental stress, living organisms accumulate extra copies of beneficial genes. The phenomenon is often referred to as gene, or genome, amplification, and it is implicated in both aging and the development of diseases like cancer.

To better understand the relationship between gene amplification, environmental stress and the aging process, scientists at Babraham Institute in Britain turned to yeast cells, an ideal model for epigenetics research. Specifically, scientists observed gene duplication in yeast exposed to high concentrations copper.

Normally, copper is toxic to yeast. But previous studies showed yeast cells can protect themselves by producing extra copies of the gene CUP1. Lab experiments showed the yeast cells can integrate additional gene copies into their chromosomes or house the copies in satellite DNA circles called extrachromosomal circular DNA, or eccDNA.

Because satellite DNA circles can be more easily acquired or quickly ditched, these extrachromosomal structures provide cells with greater genomic flexibility.

Authors of the latest study, published this week in the journal PLOS Biology, were particularly interested in determining whether the aging process influences the formation and use of eccDNA.

“This work is a continuation of our focus on understanding how cells achieve adaptability in order to be successful in challenging environments,” first study author Ryan Hull, researcher with the Babraham Institute’s epigenetics program, said in a news release. “Analyzing the creation of the eccDNA supports our finding that gene duplication can be actively driven and controlled in response to the environment, rather than random, in order to confer increased resilience to future environmental change.”

When scientists tracked the distribution of eccDNA during cell division, they found the satellite DNA was held onto by mother cells, which can produce daughter cells by dividing asymmetrically.

“It’s an intriguing phenomenon,” said study co-author Jon Houseley, the epigenetics program’s group leader. “We can liken it to a selfish insurance policy implemented by the older cells, whereby they’re hoarding these bits of DNA in the hope that they might confer an evolutionary advantage even at the cost of some inconvenience in having them around, including interference with essential cellular pathways and a likely contribution to aging.”

Previous studies suggest cancer cells can use eccDNA to boost their resilience to the detriment of the host organism’s health. These satellite DNA circles can contain drug resistance genes, which can protect the cancer cells from chemotherapy.

An improved understanding of the eccDNA formation process could help scientists design more effective cancer-targeting drug therapies.

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