Non-canonical chromatin-based functions for the threonine metabolic pathway

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Multi-functional proteins, or moonlighters, exhibit roles beyond their primary functions, challenging traditional biological paradigms.
• Crosstalk between distinct biological pathways, such as amino acid metabolism and chromatin regulation, is increasingly recognized as crucial for cellular homeostasis.

Purpose of the Study:

• To investigate novel connections between the threonine biosynthetic pathway and chromatin regulation.
• To elucidate the non-canonical functions of threonine biosynthesis enzymes in Saccharomyces cerevisiae.

Main Methods:

• Genetic analysis of threonine auxotrophs in Saccharomyces cerevisiae.
• Assessment of ribosomal DNA (rDNA) silencing phenotypes.
• Investigation of DNA repair mechanisms involving the MRX complex.

Main Results:

• The threonine biosynthetic pathway is indispensable for transcriptional silencing of ribosomal DNA (rDNA) in yeast.
• Enzymes within the pathway contribute to rDNA silencing via distinct mechanisms, with some effects rescued by exogenous threonine.
• Homoserine dehydrogenase, a key enzyme, facilitates DNA repair through interaction with the MRX complex.

Conclusions:

• The threonine biosynthetic pathway plays a critical role in both chromatin regulation and DNA repair, extending beyond its canonical metabolic function.
• These findings highlight enzymes with non-canonical roles and suggest potential applications as anti-fungal pharmaceutical targets.