How does an aging-associated enzyme access our geneticmaterial? penn_state ScienceAdvances
packaging material turns on a gene, while removing the acetyl flag turns the gene off. Sirtuins can silence gene activity by removing the acetyl flag from histones packaged into nucleosomes. Understanding how sirtuins interact with the nucleosome to remove this flag could inform future drug discovery efforts."
"We have visualized a sirtuin enzyme called SIRT6 on its physiologically relevant substrate—the entire nucleosome," said Jean-Paul Armache, assistant professor of biochemistry and molecular biology at Penn State and an author of the paper."And we found that SIRT6 interacts with multiple parts of the nucleosome, not only the histone where the acetyl flag is to be modified.
"The arginine anchor is a common paradigm for how many chromatin proteins interact with the nucleosome," said Tan."When we mutated the SIRT6 arginine anchor, the activity at the K9 position was severely affected, supporting a critical role for the SIRT6's arginine anchor. Surprisingly, this mutation also impacted SIRT6's enzymatic activity at a different position, K56, located much further away.
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