Open Close
General Information
Symbol
Dmel\lokp6
Species
D. melanogaster
Name
FlyBase ID
FBal0216721
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
mnkp6, mnk6006, chk2P6
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

The lokp6 allele contains a P-element insertion at amino acid position 52 and an associated deletion that removes 218 nucleotides of genomic sequence, including the lok start codon.

The P{} is inserted into the second exon of the long form of lok and is associated with a small deletion that includes the start codon.

Insertion components
P{}lokp6
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 ( 0 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

lokp6 homo- and heterozygous as well as lokKD/lokp6 females show a much milder loss of germline stem cells upon X-ray irradiation than wild-type controls.

Embryos at stages 4-5 from jnjΔ35/jnjΔ35 mutant mothers do not show any evidence of a "nuclear fallout" phenotype wherein faulty nuclei are actively removed into the yolk.

Mutant larvae do not show induction of apoptosis after exposure to 4000Rad irradiation, in contrast to wild-type larvae.

The presence of lokp6 partially abolishes the apoptosis usually seen in cells containing dicentric chromosomes (generated using Scer\FLP1hs.PP-induced recombination in chromosomes containing inverted Scer\FRT sites). At 12-14 hours after heat shock eye disc apoptosis is suppressed when dicentrics are generated in any of DcY-FrTr4B1A, DcYy+, P{FRT(whs)}(8F)105 or P{inv.FRT}Dc3-FrTr1D. Wing disc apoptosis is also suppressed 12-14 hours after heat shock of any of DcY-FrTr4B1A, DcYy+, DcY-H1, DcY-H2 or DcY-H3, P{FRT(whs)}(8F)105 or P{inv.FRT}Dc3-FrTr1D. However the wing disc apoptosis seen 24 hours after dicentric formation is only suppressed in Y chromosome dicentrics; apoptosis is still seen when dicentric chromosomes are induced on the X or an autosome. When dicentric chromosomes are generated in larval neuroblast cells, fewer than 40% of lokp6 mutant have a normal karyotype 96 hours following FLPase recombination (using P{inv.FRT}Dc3-FrTr1D or P{FRT(whs)}(8F)105) compared to 80-90% in the absence of lokp6. Phenotypes observed in cells with abnormal karyotypes include the presence of multiple acentric chromatids, chromosome fusions and tetraploidy.

Irradiation of lokp6 mutants with 4000 rad destroys the post-irradiation induction of apoptosis seen in wild-type flies after irradiation.

94.1% of eggs laid by mei-41D3 females have the correct number of dorsal appendages, while 2.3% have fused appendages.

Embryos derived from homozygous females do cellularise during interphase 14; a uniform monolayer of nuclei surrounded by a hexagonal network of membrane and associated actin network can be seen at this stage in the mutant embryos, as occurs in wild type. The mutant embryos also undergo gastrulation.

lokp6 mutants display a reduction in radiation-induced cell death. However, they can survive ionising radiation in the long-term just as well as wild-type flies.

The wing discs of lokp6 mutant third instar larvae exhibit reduced levels of apoptosis in response to X-ray induced irradiation with 4000 rads compared to controls. As in controls, very little apoptosis is seen in the absence of irradiation. A mild defect in cell cycle arrest is seen.

Mutant embryos assemble morphologically normal centrosomes and spindles during all of the early embryonic divisions. lokp6 mutant embryos are resistant to the DNA damaging agents, such as Bleomycin and camptothecin. When treated with Bleomycin, mutant embryos (unlike wild-type) exhibit normal looking metaphase and anaphase elongation, though the chromosomes are stretched between the spindle poles and often do not fully resolve, producing grossly abnormal daughter nuclei joined by bridges that persist into interphase. In wild-type embryos, nuclei produced by DNA damaged induced division failures consistently drop into the interior of the cortex, in lokp6 mutants however the nuclei invariably remain in the cortical monolayer following DNA damage.

Mutant egg chambers exhibit a wild-type-like metaphase I arrest. Also no increase in X chromosome nondisjunction is seen.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference

lokp6/lokp6 has cell death defective | conditional phenotype, enhanceable by mei-4129D

lokp6/lokp6 has cell death defective | conditional phenotype, enhanceable by grpfs1

NOT Enhanced by
Statement
Reference
Suppressed by
Statement
Reference

grpfs1, lokp6 has cell death defective | conditional phenotype, suppressible by grpGUS.cBa, grpfs1

Enhancer of
Statement
Reference

lok[+]/lokp6 is an enhancer of increased cell number | female | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

NOT Enhancer of
Statement
Reference
Suppressor of
Statement
Reference

lok[+]/lokp6 is a suppressor of decreased cell number | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokp6 is a suppressor of decreased cell number | female | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokp6 is a suppressor of increased cell number | female | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokKD is a suppressor of decreased cell number | female | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokKD is a suppressor of increased cell number | female | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6 is a suppressor of increased cell death phenotype of nbs1

NOT Suppressor of
Other
Phenotype Manifest In
Enhanced by
Statement
Reference

lokp6/lokp6 has eye disc | conditional phenotype, enhanceable by mei-4129D

lokp6/lokp6 has wing disc | conditional phenotype, enhanceable by mei-4129D

lokp6/lokp6 has eye disc | conditional phenotype, enhanceable by grpfs1

lokp6/lokp6 has wing disc | conditional phenotype, enhanceable by grpfs1

lokp6/lokp6 has larval neuroblast | larval stage | conditional phenotype, enhanceable by grpfs1

Enhancer of
Statement
Reference

lok[+]/lokp6 is an enhancer of cystoblast | supernumerary | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

NOT Enhancer of
Statement
Reference

lokp6 is a non-enhancer of chromosome & neuroblast | third instar larval stage 2 phenotype of mre11unspecified

lokp6 is a non-enhancer of chromosome & neuroblast | third instar larval stage 2 phenotype of tefuunspecified

Suppressor of
Statement
Reference

lok[+]/lokp6 is a suppressor of female germline stem cell | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokp6 is a suppressor of female germline stem cell | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokp6 is a suppressor of cystoblast | supernumerary | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokKD is a suppressor of female germline stem cell | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lokp6/lokKD is a suppressor of cystoblast | supernumerary | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

lok[+]/lokp6 is a suppressor of nucleus | maternal effect | embryonic stage phenotype of jnjΔ35

lok[+]/lokp6 is a suppressor of karyosome | adult stage phenotype of spn-A1

lokp6 is a suppressor of egg chamber phenotype of Rpp3018.2

lokp6 is a suppressor of dorsal appendage phenotype of CycJ+t4, arminull

lokp6 is a suppressor of embryo | maternal effect phenotype of RecQ5D1

lokp6 is a suppressor of nucleus | maternal effect phenotype of RecQ5D1

lokp6 is a suppressor of centrosome | maternal effect phenotype of RecQ5D1

lokp6/lokp6 is a suppressor of dorsal appendage phenotype of aubHN2/aubQC42

lokp6/lokp6 is a suppressor of karyosome phenotype of Brca2KO/Brca256E

lokp6, lokp6, lokp6, lokp6 is a suppressor of microtubule organizing center & oocyte phenotype of armi72.1/armi1

lokp6, lokp6, lokp6, lokp6 is a suppressor of microtubule organizing center & oocyte phenotype of spn-D2

lokp6/lokp6 is a suppressor of egg phenotype of squHE47/squPP32

lokp6/lokp6 is a suppressor of dorsal appendage phenotype of squHE47/squPP32

lokp6 is a suppressor of spindle | maternal effect phenotype of MCPH1Z1861

lokp6/lokp6 is a suppressor | partially of phenotype of Wee1ES1

lokp6/lokp6 is a suppressor of spindle | embryonic stage phenotype of grpfsA4

lokp6/lokp6 is a suppressor of chorion phenotype of spn-D1

lokp6/lokp6 is a suppressor of oocyte nucleus phenotype of spn-D1

Df(2L)pr-A14, lokp6, lokp6 is a suppressor of chorion phenotype of spn-BBU

Df(2L)pr-A14, lokp6, lokp6 is a suppressor of oocyte nucleus phenotype of spn-BBU

lokp6, lokp6, lokp6, lokp6 is a suppressor of chorion phenotype of okrAA/okrRU

lokp6, lokp6, lokp6, lokp6 is a suppressor of oocyte nucleus phenotype of okrAA/okrRU

NOT Suppressor of
Statement
Reference

lok[+]/lokp6 is a non-suppressor of karyosome | adult stage phenotype of Scer\GAL4VP16.nos.UTR, lidGLV21071

lokp6/lokp6 is a non-suppressor of karyosome phenotype of SRPK129-09/Df(2R)ED2436

Other
Statement
Reference

lokp6, nopoZ1447 has interphase & organism | embryonic cycle 11 | maternal effect phenotype

nopoZ1447/Df(2R)Exel7153, lokp6 has interphase & organism | embryonic cycle 11 | maternal effect phenotype

lokp6, nopoExc142/nopoZ1447 has interphase & organism | embryonic cycle 11 | maternal effect phenotype

Additional Comments
Genetic Interactions
Statement
Reference

Embryos at stages 4-5 from lokp6/+, jnjΔ35/jnjΔ35 double mutant mothers exhibit reduced nuclear fallout as compared to those from jnjΔ35/jnjΔ35 single mutant mothers.

The developmental delay and arrest at cycle 3 characteristic for embryos from ddbtZ4344 fathers is partially rescued in embryos from ddbtZ4344 fathers and lokp6 mothers - these embryos are allowed to progress past cycle 3 despite the number of chromosomal abnormalities they display (lagging chromosomes, anaphase bridges and nuclei with variable chromosome content).

lokp6/+ fails to suppress the abnormal karyosome morphology observed in females expressing lidGLV21071 under the control of Scer\GAL4nos.UTR.T:Hsim\VP16.

lokp6/+ suppresses the abnormal karyosome morphology observed in spn-A1 mutants.

Most egg chambers develop into eggs in Rpp3018.2 ; lokp6 double mutant females, and these eggs can be laid and fertilised.

lokp6 partially suppresses the dorsal appendage defects seen in eggs produced by armi72.1/Df(3L)armi-J mutant mothers. The number of eggs produced is also significantly increased.

lokp6 partially suppresses the dorsal appendage defects seen in eggs produced by arminull mutant mothers (expressing CycJ+t4 to restore CycJ[+] function). The number of eggs produced is also significantly increased.

lokp6 does not suppress the developmental abnormalities seen in Df(3L)armi-J mutant flies. As in Df(3L)armi-J alone, the resulting females produce no eggs and have disorganised ovarioles.

lokp6, Df(2L)HisC double mutants exhibit a Df(2L)HisC-like phenotype.

The mild abnormal spindle phenotype seen in syncytial embryos derived from homozygous DNApol-ηExc2.15 females in the absence of UV irradiation is suppressed if the females are also homozygous for lokp6. In addition, the spindle abnormalities seen after irradiation in embryos derived from homozygous DNApol-ηExc2.15 females are also suppressed in embryos derived from double mutant females.

lokp6 does not rescue the karyosome defects seen in SRPK129-09/Df(2R)ED2436 mutant oocytes.

The ventralised eggshell phenotype seen in eggs derived from homozygous CycGHR7 females is suppressed in more than 90% of eggs if the females are also carrying lokp6/Df(2L)BSC258.

The inactivation of centrosome associated with asynchronous nuclei in RecQ5D1 embryos is suppressed when maternal lokp6 is also absent from the embryo. In addition, the nuclear descent from the cortex is also suppressed.

The dorsal appendage defects seen in eggs laid by aubHN2/aubQC42 females are suppressed if the females are also homozygous for lokp6; 99.2% of the eggs have wild-type dorsal appendages.

The dorsal appendage defects seen in eggs laid by armi1/armi72.1 females are partly suppressed if the females are also homozygous for lokp6; 16.1% of the eggs have fused dorsal appendages, 7.3% lack dorsal appendages and 76.6% have wild-type dorsal appendages.

80% of eggs derived from lokp6 ; rhiKG00910/rhi02086 double mutant females have two normal dorsal appendages.

lokp6 partially suppresses the phenotype of embryos derived from nopoZ1447 females; the acentrosomal, barrel-shaped mitotic spindles are restored to normal spindles with attached centrosomes. However, DNA defects are common in embryos derived from the double mutant females, particularly during cortical divisions, with abnormal DNA aggregates that are shared by more than one spindle often being seen. The embryos derived from the double mutant females complete syncytial divisions, and arrest with aberrant morphology upon the initiation of gastrulation.

Embryos derived from lokp6 nopoZ1447 double mutant females have significantly shorter interphases during cycle 11 compared to wild-type or lokp6 single mutant embryos.

Embryos derived from lokp6 nopoZ1447/lokp6 Df(2R)Exel7153 females have significantly shorter interphases during cycle 11 compared to wild-type or lokp6 single mutant embryos.

Embryos derived from lokp6 nopoZ1447/lokp6 nopoExc142 females have significantly shorter interphases during cycle 11 compared to wild-type or lokp6 single mutant embryos.

The eggshell patterning and karyosome formation defects of Brca2KO/Brca256E females are rescued by lokp6/lokp6.

lokp6 partially suppresses the increased levels of apoptosis seen in mitotically cycling ovarian follicle cells following expression of duphsp70.T:Hsap\MYC.

mei-4129D abolishes the residual apoptotic response seen in the eye discs of lokp6 mutants containing dicentric chromosomes (generated using Scer\FLP1hs.PP-induced recombination in chromosomes containing inverted Scer\FRT sites). This effect is seen at 12-14 hours after heat shock, using either the DcYy+ or the P{inv.FRT}Dc3-FrTr1D chromosome. Wing disc apoptosis is suppressed in mei-4129D lokp6 double mutants 12-14 hours after heat shock of DcYy+ or P{inv.FRT}Dc3-FrTr1D. At 24 hours after heat shock wing disc apoptosis is suppressed in double mutant cells containing Y chromosome dicentrics, but apoptosis is still seen when dicentric chromosomes are generated on chromosome three. 25% of lokp6 mei-4129D double mutant larval neuroblast cells have normal karyotypes 48 hours after dicentric chromosomes production (generated using Scer\FLP1hs.PP-induced recombination in P{inv.FRT}Dc3-FrTr1D, which contains inverted Scer\FRT sites), whereas 44% appear normal in the dicentric controls. Phenotypes observed in cells with abnormal karyotypes include the presence of multiple acentric chromatids, chromosome fusions and tetraploidy.

grpfs1 partially suppresses the residual apoptotic response seen in lokp6 mutants containing dicentric chromosomes (generated using Scer\FLP1hs.PP-induced recombination in chromosomes containing inverted Scer\FRT sites). Eye disc apoptosis is abolished 12-14 hours after heat shock of DcYy+, P{FRT(whs)}(8F)105 or P{inv.FRT}Dc3-FrTr1D. Wing disc apoptosis is also suppressed in grpfs1 lokp6 mutants at 12-24 hours after heat shock of DcYy+, P{FRT(whs)}(8F)105 or P{inv.FRT}Dc3-FrTr1D. At 24 hours after heat shock wing disc apoptosis is suppressed in double mutant cells containing Y chromosome dicentrics, but apoptosis is still seen when dicentric chromosomes are generated on the X or autosome.

Expression of grpGUS.cBa partially suppresses the apoptosis seen in lokp6 grpfs1 double mutant cells containing dicentric chromosomes (generated using Scer\FLP1hs.PP-induced recombination in chromosomes containing inverted Scer\FRT sites). This effect is seen at 12-14 hours after heat shock of DcYy+.

The fused dorsal appendage phenotype of armi72.1/armi1 eggs is suppressed in lokp6; armi72.1/armi1 eggs with 92% of double mutants showing wild-type appendage morphology.

The fused dorsal appendage phenotype of aubHN/aubQC42 eggs is suppressed in lokp6; aubHN/aubQC42 eggs with 98% of double mutants showing wild-type appendage morphology.

The microtubule-organizing center phenotype of armi72.1/armi1 oocytes is suppressed by the lokp6 mutation.

The microtubule-organizing center phenotype of spn-D2 oocytes is suppressed by the lokp6 mutation.

The fused dorsal appendage phenotype of spn-D2 eggs is suppressed by lokp6.

The dorsoventral patterning defects seen in eggs derived from squHE47/squPP32 females are nearly completely suppressed if the females are also homozygous for lokp6; 9.3% have a single dorsal appendage or the appendages are fused at the base and 90.6% of the eggs are similar to wild type.

The mitotic defects seen in embryos derived from MCPH1Z1861 females are suppressed if the females are also mutant for lokp6; mitotic spindles are restored to near normality and the early developmental arrest is suppressed, such that most of the double mutant embryos complete syncytial divisions, cellularise and cease developing near gastrulation (most of the embryos initiate gastrulation but it is grossly aberrant). The double mutant embryos occasionally have abnormal DNA aggregates shared by more than one spindle and multipolar spindles.

A significant number of embryos derived from grpfs1 lokp6 double mutant females have a uniform monolayer of cortical nuclei surrounded by a hexagonal actin network, indicating that they have initiated or completed cellularisation. The nuclei in the double mutant embryos are larger than in wild-type controls. The double mutant embryos consistently proceed through a fifth cortical mitotic cycle (14th cycle) before cellularisation (in wild-type embryos, cellularisation occurs after the 13th cycle). The double mutant embryos also undergo gastrulation. The cephalic furrow does not form in the double mutant embryos.

grpfs1 lokp6 double mutants exhibit normal telomere protection and chromosome break repair.

Apoptosis is substantially reduced in nbs1 lokp6 double mutant third instar larval wing discs compared to nbs1 single mutants.

lokp6 mutants that are also heterozygous for Df(3L)H99 display significantly lower levels of acridine orange staining (indicating cell death) at 18 and 24 hours after irradiation compared with lokp6 mutants. By 30 hours after irradiation, however, there is a substantial increase in cell death in lokp6, Df(3L)H99/+ double mutants.

Double mutants of p535A-1-4 and lokp6 display similar levels of acridine orange staining (indicating cell death) after radiation (visualised in third instar imaginal discs irradiated with 4,000 R).

lokp6; mei-4129D mutants develop normally and males are fertile. lokp6 fails to enhance the chromosome fusion phenotype seen in the nuclei of third instar larval neuroblasts of mre11unspecified.

Mutation of lokp6 in weeES1 mutants rescues the anastral spindle and γTURC phenotypes, but fails to rescue the promiscuous spindle interaction and multipolar spindle phenotypes. The displacement of centrosomes from the cortex in interphase of cycle 12 is only partially rescued in weeES1, lokp6 double mutants.

lokp6 enhances the partial loss of cell cycle arrest seen in grpfs1 mutant third instar larval wing discs in response to X-ray induced irradiation. No arrest is seen in the double mutant larvae.

Cellularisation and cortical retention of DNA is partially restored in weeES1 lokp6 double mutant embryos and about 60% of the double mutant embryos show evidence of migration changes that normally occur in cellularised embryos (such as the migration of pole cells toward the embryo anterior). The extent of this rescue is variable and none of the double mutant embryos survive to hatching. The distribution and appearance of DNA in these embryos is abnormal.

Xenogenetic Interactions
Statement
Reference

The loss of germline stem cells (GSCs) observed upon heat-shock induced expression of Crei\I-CreIhs.PR (to introduce DNA damage) is rescued by combination with lokp6 or lokKD in hetero-, homo- or transheterozygosity as these double mutant flies contain significantly higher number of GSCs both at 3 days and 1 week post heat-shock compared to Crei\I-CreIhs.PR single mutants.

lokKD/lokp6;Crei\I-CreIhs.PR mutants have more GSCs than wild-type controls even without the induction of DNA damage by heat-shock.

Crei\I-CreIhs.PR germaria in which DNA damage has been evoked by heat-shock accumulate cystoblast-like single cells and this accumulation is accelerated by lokp6 or lokKD heterozygosity (significantly increased number of CB-like cells observed already at 3 days post heat-shock). By contrast, both lokp6 or lokKD homo- or transheterozygosity completely abolishes the CB-like cell accumulation phenotype.

A lokp6 mutant background cannot alleviate the overgrowth or anterior cell cycle arrest of wing discs with posterior 'undead' Scer\GAL4hh-Gal4>WScer\UAS.cYa, BacA\p35Scer\UAS.cHa cells.

Complementation and Rescue Data
Comments

Expression of lok+tBa rescues the partial suppression of apoptosis seen in lokp6 mutant cells containing dicentric chromosomes (generated using Scer\FLP1hs.PP-induced recombination in chromosomes containing inverted Scer\FRT sites).

Expression of lok+tBa rescues the reduction in X-ray induced radiation seen in lokp6 mutant third instar larvae.

Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (8)
References (40)