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

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Title: Systematic triple-mutant analysis uncovers functional connectivity between pathways involved in chromosome regulation
Authors: Haber, James E.
Braberg, Hannes
Wu, Qiuqin
Ryan, Colm J.
et al.
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Date: Jun-2013
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.
Type of material: Journal Article
Publisher: Elsevier
Journal: Cell reports
Volume: 3
Issue: 6
Start page: 2168
End page: 2178
Copyright (published version): 2013 The Authors
Keywords: Genetic interactionsTriple-mutant analysisRdh54
DOI: 10.1016/j.celrep.2013.05.007
Language: en
Status of Item: Peer reviewed 2013-08-01T15:09:37Z
Appears in Collections:Computer Science Research Collection

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