Altered S-AdenosylMethionine availability impacts dNTP pools in Saccharomyces cerevisiae

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Saccharomyces cerevisiae is a model organism for studying genome instability.
• AdoMet synthetases (SAM1, SAM2) generate S-AdenosylMethionine (AdoMet), crucial for methylation and linked to the folate and methyl cycles.
• Previous studies showed SAM1 and SAM2 deletions impact AdoMet levels and genome instability differently.

Purpose of the Study:

• Investigate the relationship between AdoMet levels, dNTP pools, and genome instability in sam2∆/sam2∆ yeast cells.
• Determine how altered AdoMet metabolism affects deoxyribonucleotide triphosphate (dNTP) synthesis and stability.

Main Methods:

• Comparative analysis of dNTP levels in wildtype and sam2∆/sam2∆ Saccharomyces cerevisiae strains.
• Assessment of genome instability markers in relation to observed dNTP pool alterations.

Main Results:

• sam2∆/sam2∆ cells exhibit lower AdoMet levels and increased genome instability compared to wildtype.
• These cells show elevated levels of dATP, dCTP, and dGTP, contributing to a larger overall dNTP pool.
• dTTP levels were not significantly altered in the sam2∆/sam2∆ cells.

Conclusions:

• The elevated dNTP pool in sam2∆/sam2∆ cells, resulting from altered AdoMet metabolism, likely contributes to increased genome instability.
• Uncontrolled dNTP levels can lead to DNA damage, explaining the observed instability in these yeast mutants.