Danish Cancer Institute shared a post on LinkedIn:
“New discovery: How cells keep our DNA safe and organised
Scientists at the Danish Cancer Institute have uncovered a hidden mechanism that helps cells maintain the health and organisation of their DNA. The study, led by Professor Niels Mailand and published in The EMBO Journal, reveals a key system that protects the integrity of the epigenome – how the genome is packaged and regulated within the cell.
“Our study provides a holistic picture of how different types of ubiquitin signals keep cellular processes in check. By decoding and manipulating these molecular signals, we can build a better understanding of their functions—and how their misregulation impacts diseases like cancer,” said Professor Mailand.
Every cell in the body must carefully control which genes are switched on and which are kept silent. One of the proteins that helps do this is SUV39H1, which promotes the compaction of certain regions of DNA to keep them inactive. But when SUV39H1 is not properly regulated, it can disrupt the organisation of the genome and have serious consequences.
The researchers discovered that cells use a very specific kind of molecular tag – called K29-linked ubiquitylation – to label SUV39H1 for timely removal. Without this system, cells accumulate too much SUV39H1 protein, which can lead to imbalances in gene activity.
When this control mechanism fails, gene regulation can go awry and may ultimately contribute to cancer development.
“Uncontrolled changes in the way our DNA is packaged and read are a hallmark of many cancers,” said Professor Mailand. “Understanding how cells prevent excessive accumulation and activity of proteins that impact DNA compaction and gene silencing gives us important insight into how these processes go wrong in cancer. It may also open new opportunities to target them in the future.”
This discovery not only reveals a previously unknown safeguard in the cell’s regulatory system that manage proteins but also provides valuable new tools for studying how specific protein tags affect genome stability and other cellular processes.”
Title: Functional landscape of ubiquitin linkages couples K29-linked ubiquitylation to epigenome integrity
Authors: Javier Arroyo-Gomez, Matthew J Murray, Claire Guérillon, Juanjuan Wang, Ekaterina Isaakova, Nazaret Reverón-Gómez, Mikaela Koutrouli, Aldwin Suryo Rahmanto, Katrine Mitrofanov, Andreas Ingham, Sofie Schovsbo, Katrine Weischenfeldt, Fabian Coscia, Dimitris Typas, Moritz Völker-Albert, Victor Solis, Lars Juhl Jensen, Anja Groth, Andreas Mund, Petra Beli, Robert F Shearer and Niels Mailand
Read the findings in full: The EMBO Journal.
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