Abstract
We have devised a genetic screen, termed synthetic dosage lethality, in which a cloned 'reference' gene is inducibly overexpressed in a set of mutant strains carrying potential 'target' mutations. To test the specificity of the method, two reference genes, (CTF13, encoding a centromere binding protein, and ORC6, encoding a subunit of the origin of replication binding complex, were overexpressed in a large collection of mutants defective in either chromosome segregation or replication. CTF13 overexpression caused synthetic dosage lethality in combination with ctf14-42 (cbf2, ndc10), ctf17-61 (ch14), ctf19-58 and ctf19-26. ORC6 overexpression caused synthetic dosage lethality in combination with cdc2-1, cdc6-1, cdc 14-1, cdc16-1. These relationships reflect specific interactions, as overexpression of CTF13 caused lethality in kinetochore mutants and overexpression of ORC6 caused lethality in replication mutants. In contrast, only one case of dosage suppression was observed. We suggest that synthetic dosage lethality identifies a broad spectrum of interacting mutations and is of general utility in detecting specific genetic interactions using a cloned wild-type gene as a starting point. Furthermore, synthetic dosage lethality is easily adapted to the study of cloned genes in other organisms.
| Original language | English |
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| Pages (from-to) | 95-102 |
| Number of pages | 8 |
| Journal | Genetics |
| Volume | 143 |
| Issue number | 1 |
| State | Published - May 1996 |
Funding
We thank SUSAN MICHAELIS andJAsPER RINE for helpful comments on the manuscript and members of our labs for helpful discussions. P.H. was supported in part by National Institutes of Health grant CA16519, and J.J.L. was supported in part by the Lucille P. Markey Charitable Trust and the Rita Allen Foundation.
| Funder number |
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| P01CA016519 |