| Citation |
Brumby, A., Secombe, J., Horsfield, J., Coombe, M., Amin, N., Coates, D., Saint, R., Richardson, H. (2004). A genetic screen for dominant modifiers of a cyclin E hypomorphic mutation identifies novel regulators of S-phase entry in
Drosophila. Genetics 168(1): 227--251.
(Export to RIS)
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| PubMed 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.
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