Cells need both genomes to be in sync to tango

A new Hudson Institute study has uncovered how two genomes within the same cell need to work together for human cells to function effectively, with implications for cancer treatment and testing.

Professor Justin St John

The team, led by Professor Justin St. John with PhD student Claire Sun and research assistant Jacqui Johnson, looked at the effects of two different factors called DNA demethylation agents on cell samples of human glioblastoma, a type of brain tumour.

They found that these agents had an impact on mitochondrial DNA within the tumour cells.

The study, published in the journal Nucleic Acids Research, suggests two genomes within a cell – the mitochondrial genome (which houses genes that provide power for cells) and the nuclear genome (which we know as our DNA) – need to establish harmony for the cell to function effectively.

Working in sync

The study shows the two genomes must work together – or disease may develop.

“If one of the genomes is out of sync with the other, then cells don’t function effectively or they could become disease-like,” Prof St. John explained.

“We discovered that the levels of harmony between the two genomes are controlled by the levels of methylation – a mechanism cells use to turn genes on or off – within each cell.”

Decluttering disease messages

The research could also explain how cancer treatments using DNA demethylation agents, which are currently in clinical trials for different types of cancer, work. These drugs could ‘reset’ methylation levels of both genomes within a cell to ‘declutter’ the messages they produce, enabling them to communicate and potentially stop them from becoming cancerous.

Tests used in cancer research and diagnostics to analyse methylation and ‘map out’ potential tumour pathways within cells, might not have been showing all of the picture, Prof St. John said.

“Our research provides strong evidence that the mitochondrial genome may also undergo methylation. However, the results of methylation assays either do not cover the mitochondrial genome or they ignore the mitochondrial genome because it was previously thought of as not being important,” he said.

“These results suggest that analysis of DNA methylation levels should also include analysis of the mitochondrial genome, not just the nuclear genome – to provide a comprehensive analysis of DNA methylation levels. This will help to show if the cells have synchronised both genomes to communicate effectively and if the failed communication is contributing to disease.”

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