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Analysis of N-glycan glucosylation and processing using a synthetic lethal approach

A large-scale procedure was used to screen for deletions affecting growth of Saccharomyces cerevisiae when combined to ALG6 , ALG88, ALG10, CWH41, ROT2 or CNE1 deletions. 40 genes, grouped in 8 functional categories, were found to interact with the 6 query genes. The resulting network of 61 synthetic interactions was composed of 3 subnetworks, the N-glucosyltransferase (ALG6, ALG8, ALG10), the glucosidase (CWH41, ROT2) and CNE1 interaction sets, respectively. Deletion in 34 interacting genes conferred calcofluor white hypersensitivity, strengthening the relationship between N-glycan glucosylation/processing and cell wall physiology. In addition, a genetic interaction was found between ALG6 and SEC53, the yeast homologues of human ALG6 and PMM2 genes involved in congenital disorders of glycosylation. The alg6sec53 double mutant shows a synthetic growth defect and a CPY underglycosylation. Since this synthetic interaction is conserved from yeast to mammals, this work proposes the use of SGA analysis as a tool to uncover digenic effects that may underlie complex human genetic disorders.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.80336
Date January 2003
CreatorsMunyana, Christella
ContributorsBussey, Howard (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Biology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 002102060, proquestno: AAIMQ98705, Theses scanned by UMI/ProQuest.

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