FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Allele: Dmel\Orc635
Open Close
General Information
Symbol
Dmel\Orc635
Species
D. melanogaster
Name
FlyBase ID
FBal0241167
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
Nature of the Allele
Progenitor genotype
Caused by aberration
Cytology
Description

Imprecise excision of P{EPgy2}EY04071 (mapped 71bp upstream of the Orc6 start codon) results in deletion of the whole Orc6 coding region and some of CG1667.

Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

In Orc635 homozygotes, brains are underdeveloped; larval neuroblasts show prevalent karyotype defects, namely chromosomes with missing parts, aberrantly condensed, and fragmented.

The larval brain of Orc635/Orc635, Orc6K23E.Orc6.UAS.GFP/Orc6K23E.Orc6.UAS.GFP is underdeveloped. The surviving adult frequently exhibit missing/defective scutellar bristles and a small and misshaped eye.

Orc635 mutants are lethal and die during third instar larval stage; on the cellular level they display chromosomal abnormalities in larval brain cells.

The optic lobes of Orc635 mutant brains are significantly smaller in size compared with the wild-type or heterozygous animals. BrdU incorporation is also severely reduced in homozygous Orc635 mutant larval brains compared with the large levels of BrdU incorporation in heterozygous brains, demonstrating the lack of DNA replication. No imaginal discs are detected in late third instar larvae of Orc635 mutant animals.

Orc635 mutant salivary glands appear morphologically normal, but are reduced in size. BrdU incorporation in salivary glands is close to the levels of the wild-type or heterozygous animals, suggesting that DNA replication is not affected by the deletion of Orc6.

Orc635 mutant cells are delayed in cell cycle progression. The ratio of G1 cells (with a single centrosome) to G2 cells (with 2 centrosomes) is increased by a factor of approximately 7 in Orc635 mutants.

Overall, the number of mitotic cells observed in Orc635 mutants decreased compared with wild-type or heterozygous tissues. No cells at anaphase or telophase stages are found in cells carrying the Orc635 deletion. Instead, a large number of metaphase-like figures are observed, in which highly condensed chromosomes are present with incomplete or disorganised alignments. In addition, individual chromatids appear aberrantly condensed and fragmented. Mitotic chromosomes in mutant neuroblasts appear shorter and thicker than in wild-type and sister chromatid cohesion is frequently lost. Extensive chromosome fragmentation is also observed.

Chromosomes from neuroblasts isolated from Orc635 mutants carrying Orc6ΔC.220.T:Avic\GFP are able to incorporate BrdU, and therefore are able to replicate DNA. Brains observed in these larvae are significantly reduced in size compared with heterozygous or wild-type larval brains, suggesting severe defects in cell proliferation and larval brain development.

Orc635 mutant neuroblasts carrying Orc6ΔC.220.T:Avic\GFP accumulate at mitosis. The number of mitotic neuroblasts derived from these transgenic flies increases approximately 4-fold compared with Orc635 mutant cells.

A large number of metaphase-like figures are observed in Orc635 mutant cells expressing Orc6ΔC.220.T:Avic\GFP. Cells in other stages are also found (e.g. anaphase-like figures are found, containing broken chromosomes), some polyploid with multiple centrosomes, while others exhibit multiple centrosomes but don't have any DNA present.

Chromosomes from neuroblasts isolated from Orc635 mutants carrying Orc6W228A.K229A.T:Avic\GFP are able to incorporate BrdU, and therefore are able to replicate DNA. Brains observed in these larvae are significantly reduced in size compared with heterozygous or wild-type larval brains, suggesting severe defects in cell proliferation and larval brain development.

Orc635 mutant neuroblasts carrying Orc6W228A.K229A.T:Avic\GFP accumulate at mitosis. The number of mitotic neuroblasts derived from these transgenic flies increases approximately 8-fold compared with Orc635 mutant cells.

A large number of metaphase-like figures are observed in Orc635 mutant cells expressing Orc6W228A.K229A.T:Avic\GFP. Cells in other stages are also found (e.g. anaphase-like figures are found, containing broken chromosomes), some polyploid with multiple centrosomes, while others exhibit multiple centrosomes but don't have any DNA present.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Suppressed by
Statement
Reference
NOT suppressed by
Other
Statement
Reference
Phenotype Manifest In
Enhanced by
Statement
Reference
Suppressed by
NOT suppressed by
Other
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

Expression of Hsap\ORC6T:Avic\GFP does not rescue viability in Orc635 mutants (that die at the third instar larval stage).

Expression of Hsap\ORC6T:Avic\GFP results in the release of Orc635 mutant cells from G1 arrest, as shown by the ratio of cells containing either 1 or 2 centrosomes being indistinguishable from cells obtained from heterozygous siblings.

Chromosomes from neuroblasts isolated from Orc635 mutants carrying Hsap\ORC6T:Avic\GFP are able to incorporate BrdU, and therefore are able to replicate DNA. Brains observed in these larvae are significantly reduced in size compared with heterozygous or wild-type larval brains, suggesting severe defects in cell proliferation and larval brain development.

Orc635 mutant neuroblasts carrying Hsap\ORC6T:Avic\GFP accumulate at mitosis. The number of mitotic neuroblasts derived from these transgenic flies increases approximately 2-fold compared with Orc635 mutant cells.

Complementation and Rescue Data
Comments

Expression of Orc6Y225S.Orc6.Scer\UAS.T:Avic\GFP under its native promoter fails to rescue the third instar lethality in Orc635 mutant larvae but expression under the control of Scer\GAL4tub.PU can partially restore the viability of the Orc635 mutants. The rescued adults, however, display several phenotypic defects compared to controls including upheld wing posture, missing posterior scutellar bristles, rough spots in the eye and irregular hair pattern on the abdomen.

Larvae expressing Orc6Y225S.Orc6.Scer\UAS.T:Avic\GFP under the control of its native promoter in Orc635 mutant background display decreased levels of DNA replication in both neural ganglia and testes compared to controls.

Expression of Orc6Y225S.Orc6.Scer\UAS.T:Avic\GFP from its native promoter does not rescue the aberrant karyotype characteristic for Orc635 and the chromosomes in larval brain cells display a number of defects including loss of arms, fragmentation, polyploidy, aberrant condensation or misalignment during the cell cycle. This abnormal karyotype is however rescued when Orc6Y225S.Orc6.Scer\UAS.T:Avic\GFP is expressed under the control of the Scer\GAL4tub.PU driver.

Expression of Orc6Orc6.Scer\UAS.T:Avic\GFP under the control of its native promoter or the Scer\GAL4tub.PU driver almost completely restores the viability of Orc635 mutants. The abnormal brain cell karyotype as well as the DNA replication defects observed in brain and testes of Orc635 third instar larvae are also rescued by Orc6Orc6.Scer\UAS.T:Avic\GFP expression from its native promoter.

Expression of Orc6Y225F.Orc6.Scer\UAS.T:Avic\GFP under the control of its native promoter or Scer\GAL4tub.PU in the Orc635 mutant background partially rescues the third instar stage lethality.

Expression of Orc6D224A.Y225A.Orc6.Scer\UAS.T:Avic\GFP under its native promoter fails to rescue the third instar lethality in Orc635 mutant larvae but expression under the control of Scer\GAL4tub.PU can partially restore the viability of the Orc635 mutants and rescues their aberrant karyotype.

Expression of Orc6W228A.K229A.Orc6.Scer\UAS.T:Avic\GFP under the control of either its native promoter or the Scer\GAL4tub.PU driver does not rescue either the third instar stage lethality or the aberrant karyotype of Orc635 mutant larvae.

Expression of Orc6ΔC.200.Orc6.Scer\UAS.T:Avic\GFP under the control of either its native promoter or the Scer\GAL4tub.PU driver does not rescue either the third instar stage lethality or the aberrant karyotype of Orc635 mutant larvae.

Expression of Orc6T:Avic\GFP results in the release of Orc635 mutant cells from G1 arrest, as shown by the ratio of cells containing either 1 or 2 centrosomes being indistinguishable from cells obtained from heterozygous siblings.

Expression of Orc6+t3.3 results in the release of Orc635 mutant cells from G1 arrest, as shown by the ratio of cells containing either 1 or 2 centrosomes being indistinguishable from cells obtained from heterozygous siblings.

Expression of Orc6ΔC.220.T:Avic\GFP results in the release of Orc635 mutant cells from G1 arrest, as shown by the ratio of cells containing either 1 or 2 centrosomes being indistinguishable from cells obtained from heterozygous siblings.

Chromosomes from neuroblasts isolated from Orc635 mutants carrying Orc6ΔC.220.T:Avic\GFP are able to incorporate BrdU, and therefore are able to replicate DNA. Brains observed in these larvae are significantly reduced in size compared with heterozygous or wild-type larval brains, suggesting severe defects in cell proliferation and larval brain development.

Orc635 mutant neuroblasts carrying Orc6ΔC.220.T:Avic\GFP accumulate at mitosis. The number of mitotic neuroblasts derived from these transgenic flies increases approximately 4-fold compared with Orc635 mutant cells.

A large number of metaphase-like figures are observed in Orc635 mutant cells expressing Orc6ΔC.220.T:Avic\GFP. Cells in other stages are also found (e.g. anaphase-like figures are found, containing broken chromosomes), some polyploid with multiple centrosomes, while others exhibit multiple centrosomes but don't have any DNA present.

Expression of Orc6ΔC.200.T:Avic\GFP fails to release of Orc635 mutant cells from G1 arrest.

Orc635 mutants carrying the Orc6ΔC.200.T:Avic\GFP transgene do not differ from Orc635 mutant cells, in terms of having no BrdU incorporation in brain neuroblasts.

Expression of Orc6W228A.K229A.T:Avic\GFP results in the release of Orc635 mutant cells from G1 arrest, as shown by the ratio of cells containing either 1 or 2 centrosomes being indistinguishable from cells obtained from heterozygous siblings.

Chromosomes from neuroblasts isolated from Orc635 mutants carrying Orc6W228A.K229A.T:Avic\GFP are able to incorporate BrdU, and therefore are able to replicate DNA. Brains observed in these larvae are significantly reduced in size compared with heterozygous or wild-type larval brains, suggesting severe defects in cell proliferation and larval brain development.

Orc635 mutant neuroblasts carrying Orc6W228A.K229A.T:Avic\GFP accumulate at mitosis. The number of mitotic neuroblasts derived from these transgenic flies increases approximately 8-fold compared with Orc635 mutant cells.

A large number of metaphase-like figures are observed in Orc635 mutant cells expressing Orc6W228A.K229A.T:Avic\GFP. Cells in other stages are also found (e.g. anaphase-like figures are found, containing broken chromosomes), some polyploid with multiple centrosomes, while others exhibit multiple centrosomes but don't have any DNA present.

Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (3)
Reported As
Name Synonyms
Secondary FlyBase IDs
    References (6)