PROTOCOLS
Below are common techniques we perform in our lab.
Cycloheximide Chase
Measure OD600 of O/N cultures.
Dilute cultures to 0.2 in 10 mL. Allow to grow to mid-log phase (OD600 = 0.8-1.2 or ~6 hours).
Collect 7.5 OD units of each culture in a 15 ml conical tube and centrifuge for 2 minutes at 5000 rpm.
Resuspend each cell pellet in 3 ml pre-warmed 30°C media.
Incubate 5 min at 30°C on a heat block or in water bath.
Add 50 µL ice-cold 20X Stop mix (200 mM NaN3, 5 mg/ml BSA) to separate microcentrifuge tubes (will use in following steps). Will need 1 tube of stop mix per time point per yeast strain.
After the 5 minute incubation, add cycloheximide to final concentration of 0.25 mg/ml (37.5 µl of 20 mg/ml stock in ethanol) to each 3 ml resuspended yeast strain. CHASE HAS STARTED.
Take 950 µl (~2.5 OD600) aliquots of cells at each time point and add aliquots to appropriate centrifuge tube containing the 50 µl ice-cold 20X Stop mix. Vortex, and place on ice until the end of the chase. Time 0 needs to be collected right after adding the cycloheximide to the cell sample.
Keep samples being chased on the 30°C heating block, and vortex every ~5-10 min. Collect the remaining time points at the correct time.
At the end of chase, centrifuge all cells for 30 sec at 7000 rpm.
Aspirate supernatant and store pellets at -20°C or proceed to cell lysis.
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If you use this protocol in your studies, please cite:
Buchanan BW, Lloyd ME, Engle SM, Rubenstein EM. Cycloheximide chase analysis of protein degradation in Saccharomyces cerevisiae. Journal of Visualized Experiments 110 (e53975), 2016.
Growth Assay
Measure OD600 of O/N cultures.
Determine 0.2 OD units.
In a 96-well plate, add fresh sterile water with calculated 0.2 OD units up to 200 ul for each culture in column 1.
Add 125 ul of fresh sterile water to columns 2-4.
Perform six-fold serial dilutions, transferring 25 ul from the first column to the second, from the second to the third, and the third to the fourth.
Plate 4 ul of each well, in order, onto appropriate plates using template and multichannel pipette (in duplicate).
Incubate plates (when dry) at 30°C.
Image plates each day following growth assay until cell growth is visible up to the last column (keep incubating at 30°C).
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If you use this protocol in your studies, please cite:
Watts SG, Crowder JJ, Coffey SC, Rubenstein EM. Growth-based determination and biochemical confirmation of genetic requirements for protein degradation in Saccharomyces cerevisiae. Journal of Visualized Experiments 96 (e52428), 2015.
Lithium Acetate Transformation of Yeast
Grow yeast cells O/N at 30°C in YPD liquid media.
For each transformation, centrifuge 500 uL of yeast at 5000 rpm for 2 minutes at RT. Remove media supernatant.
Resuspend cell pellet in 1 mL of sterile water, repeat centrifuge, and remove media supernatant.
Resuspend yeast in 50 uL sterile 1X LTE.
To each transformation tube add:
4 uL carrier DNA (salmon sperm) (5 mg/ml sperm solution)
1 uL DNA from miniprep or 1 uL of sterile water for no DNA control
Mix by vortexing, and incubate at RT for 30 minutes.
Add 400 uL of 40% PEG in 1X LTE, mix by vortexing, incubate at RT for several hours (sometimes O/N).
Spin down cells at 5000 rpm for 2 minutes, remove supernatant.
Resuspend pellet in 50 uL of 1M Sorbitol.
Spread entire suspension onto selective plate, incubate at 30°C for 3-5 days.