High-throughput replica-pinning approach to screen for yeast genes controlling low-frequency events

Saccharomyces cerevisiae is a leading model system for genome-wide screens, but low-frequency events (e.g., point mutations, recombination events) are difficult to detect with existing approaches. Here, we describe a high-throughput screening technique to detect low-frequency events using high-throughput replica pinning of high-density arrays of yeast colonies. This approach can be used to screen genes that control any process involving low-frequency events for which genetically selectable reporters are available, e.g., spontaneous mutations, recombination, and transcription errors. For complete details on the use and execution of this protocol, please refer to (Novarina et al., 2020a, 2020b). [Display omitted] •Genome-wide screening to identify genes controlling low-frequency events in yeast•Applicable to any such events for which there is a selectable genetic reporter•Semi-quantitative estimation of low-frequency events rate for each strain Saccharomyces cerevisiae is a leading model system for genome-wide screens, but low-frequency events (e.g., point mutations, recombination events) are difficult to detect with existing approaches. Here, we describe a high-throughput screening technique to detect low-frequency events using high-throughput replica pinning of high-density arrays of yeast colonies. This approach can be used to screen genes that control any process involving low-frequency events for which genetically selectable reporters are available, e.g., spontaneous mutations, recombination, and transcription errors.