PMID- 8722765
OWN - NLM
STAT- MEDLINE
DCOM- 19961011
LR  - 20210915
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 143
IP  - 1
DP  - 1996 May
TI  - Establishing genetic interactions by a synthetic dosage lethality phenotype.
PG  - 95-102
AB  - 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 (chl4), ctf19-58 and ctf19-26. 
      ORC6 overexpression caused synthetic dosage lethality in combination with cdc2-1, 
      cdc6-1, cdc14-1, cdc16-1 and cdc46-1. 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.
FAU - Kroll, E S
AU  - Kroll ES
AD  - Department of Molecular Biology and Genetics, Johns Hopkins University, School of 
      Medicine, Baltimore, Maryland 21205, USA.
FAU - Hyland, K M
AU  - Hyland KM
FAU - Hieter, P
AU  - Hieter P
FAU - Li, J J
AU  - Li JJ
LA  - eng
GR  - CA-16519/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
SB  - IM
MH  - *Gene Dosage
MH  - *Genes, Fungal
MH  - *Genes, Lethal
MH  - Genes, Synthetic
MH  - Genetic Techniques
MH  - Genotype
MH  - Phenotype
MH  - Plasmids
MH  - Saccharomyces cerevisiae/*genetics/growth & development
PMC - PMC1207298
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
PMCR- 1996/08/01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
PHST- 1996/08/01 00:00 [pmc-release]
AID - 143195 [pii]
AID - 10.1093/genetics/143.1.95 [doi]
PST - ppublish
SO  - Genetics. 1996 May;143(1):95-102. doi: 10.1093/genetics/143.1.95.