Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2013 Jun 27;3(6):2168-78. doi: 10.1016/j.celrep.2013.05.007. Epub 2013 Jun 6.

Systematic triple-mutant analysis uncovers functional connectivity between pathways involved in chromosome regulation.

Author information

1
Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Waltham, MA 02454, USA. haber@brandeis.edu

Abstract

Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed triple-mutant analysis (TMA). We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered through traditional double-mutant analyses.

PMID:
23746449
PMCID:
PMC3718395
DOI:
10.1016/j.celrep.2013.05.007
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center