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https://hdl.handle.net/2440/3006
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Type: | Journal article |
Title: | A genetic screen for dominant modifiers of a cyclin E hypomorphic mutation identifies novel regulators of S-Phase entry in Drosophila |
Author: | Brumby, A. Secombe, J. Horsfield, J. Coombe, M. Amin, N. Coates, D. Saint, R. Richardson, H. |
Citation: | Genetics: a periodical record of investigations bearing on heredity and variation, 2004; 168(1):227-251 |
Publisher: | Genetics |
Issue Date: | 2004 |
ISSN: | 0016-6731 1943-2631 |
Organisation: | Centre for the Molecular Genetics of Development |
Statement of Responsibility: | Anthony Brumby, Julie Secombe, Julie Horsfield, Michelle Coombe, Nancy Amin, Deborah Coates, Robert Saint , and Helena Richardson |
Abstract: | Cyclin E together with its kinase partner Cdk2 is a critical regulator of entry into S phase. To identify novel genes that regulate the G1- to S-phase transition within a whole animal we made use of a hypomorphic cyclin E mutation, DmcycEJP, which results in a rough eye phenotype. We screened the X and third chromosome deficiencies, tested candidate genes, and carried out a genetic screen of 55,000 EMS or X-ray-mutagenized flies for second or third chromosome mutations that dominantly modified the DmcycEJP rough eye phenotype. We have focused on the DmcycEJP suppressors, S(DmcycEJP), to identify novel negative regulators of S-phase entry. There are 18 suppressor gene groups with more than one allele and several genes that are represented by only a single allele. All S(DmcycEJP) tested suppress the DmcycEJP rough eye phenotype by increasing the number of S phases in the postmorphogenetic furrow S-phase band. By testing candidates we have identified several modifier genes from the mutagenic screen as well as from the deficiency screen. DmcycEJP suppressor genes fall into the classes of: (1) chromatin remodeling or transcription factors; (2) signaling pathways; and (3) cytoskeletal, (4) cell adhesion, and (5) cytoarchitectural tumor suppressors. The cytoarchitectural tumor suppressors include scribble, lethal-2-giant-larvae (lgl), and discs-large (dlg), loss of function of which leads to neoplastic tumors and disruption of apical-basal cell polarity. We further explored the genetic interactions of scribble with S(DmcycEJP) genes and show that hypomorphic scribble mutants exhibit genetic interactions with lgl, scab (alphaPS3-integrin--cell adhesion), phyllopod (signaling), dEB1 (microtubule-binding protein--cytoskeletal), and moira (chromatin remodeling). These interactions of the cytoarchitectural suppressor gene, scribble, with cell adhesion, signaling, cytoskeletal, and chromatin remodeling genes, suggest that these genes may act in a common pathway to negatively regulate cyclin E or S-phase entry. |
Keywords: | Eye Chromosomes Animals Drosophila melanogaster Cyclin E Drosophila Proteins Membrane Proteins DNA Mutational Analysis Signal Transduction S Phase Chromatin Assembly and Disassembly Phenotype Mutation Genes, cdc Genes, Suppressor |
DOI: | 10.1534/genetics.104.026617 |
Published version: | http://www.genetics.org/cgi/content/abstract/168/1/227 |
Appears in Collections: | Aurora harvest 2 Centre for the Molecular Genetics of Development publications Molecular and Biomedical Science publications |
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