Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 1, Issue -, Pages -Publisher
WILEY
DOI: 10.1038/msb4100034
Keywords
congruence score; function prediction; quantitative phenotype; synthetic lethality; yeast
Categories
Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR020839] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG002432] Funding Source: NIH RePORTER
- NCRR NIH HHS [RR020839, U54 RR020839] Funding Source: Medline
- NHGRI NIH HHS [R01 HG002432, HG02432] Funding Source: Medline
Ask authors/readers for more resources
We predicted gene function using synthetic lethal genetic interactions between null alleles in Saccharomyces cerevisiae. Phenotypic and protein interaction data indicate that synthetic lethal gene pairs function in parallel or compensating pathways. Congruent gene pairs, defined as sharing synthetic lethal partners, are in single pathway branches. We predicted benomyl sensitivity and nuclear migration defects using congruence; these phenotypes were uncorrelated with direct synthetic lethality. We also predicted YLL049W as a new member of the dynein-dynactin pathway and provided new supporting experimental evidence. We performed synthetic lethal screens of the parallel mitotic exit network ( MEN) and Cdc14 early anaphase release pathways required for late cell cycle. Synthetic lethal interactions bridged genes in these pathways, and high congruence linked genes within each pathway. Synthetic lethal interactions between MEN and all components of the Sin3/Rpd3 histone deacetylase revealed a novel function for Sin3/Rpd3 in promoting mitotic exit in parallel to MEN. These in silico methods can predict phenotypes and gene functions and are applicable to genomic synthetic lethality screens in yeast and analogous RNA interference screens in metazoans.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available