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General Information
Symbol
Dmel\p535A-1-4
Species
D. melanogaster
Name
FlyBase ID
FBal0138188
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
dp535A-1-4, Dmp535A-1-4
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
deletion
Comment:

p53[5A-1-4] is a 3498 bp deletion that removes most of p53.

Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

3498bp deletion (coordinates 3R:23050029..23053526 ).

Deletion in the p53 locus.

3.3kb deletion in the p53 gene.

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 )
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

p535A-1-4 adults are show a severely increased sensitivity to paraquat-induced oxidative stress, as compared to controls. In agreement, whole body homogenates show higher levels of apoptosis markers (cleaved Dcp1 and cleaved Casp3) than controls only upon paraquat treatment. However, the adult brain of p535A-1-4 mutants show increased levels of apoptosis (cleaved casp3) under both paraquat treatment and basal conditions, although higher in the paraquat treatment condition.

p535A-1-4 homozygotes exhibit a severe increase in the proportion of hyperplastic testes as compared to controls; the apical tip of these testes exhibit a significant decrease in necrosis (shown by the number of spermatogonial cysts bearing Propidium Iodine-positive or TUNEL-positive cells), but no changes in the frequency of mitotic cells, as compared to controls.

p535A-1-4 homozygous adults have increased mortality rate following oral infection with Drosophila C virus; they also have significantly increased levels of virus (qRT-PCR) at 3 days post-infection.

p535A-1-4 suppresses the eye ablation phenotype resulting from an irreparable DNA double-stranded break in the BARTL (Bar and Telomere Loss) assay, such that the flies have wild-type eyes.

Within 4 h after irradiation, the imaginal discs of homozygous p535A-1-4 larvae have very few apoptotic cells compared with wild-type.

p535A-1-4 mutant flies exhibit a reduction in survival following acute starvation during early adulthood (1-2 days).

p535A-1-4/p535A-1-4 flies do not show any visible wing defects compared to wild type controls.

p535A-1-4 mutant wing disc clones grow to a much larger size than control cell clones.

p535A-1-4 mutant wing disc cells or fat body cells exhibit disrupted mitochondrial morphology, with a variety of shapes including globules and donut shapes as well as long filaments, as seen in wild-type.

Expression of p53Scer\UAS.Dp53 under the control of Scer\GAL4Bx-MS1096 induces apoptosis in wing discs. A small increase in cell proliferation is seen compared to controls, but less than is seen when p53Scer\UAS.DΔNp53 is expressed. An increase in apoptosis is also seen when p53Scer\UAS.Dp53 is expressed in a p535A-1-4 mutant background.

Expression of p53Scer\UAS.DΔNp53 under the control of Scer\GAL4Bx-MS1096 induces apoptosis in wing discs. Increased cell proliferation is seen compared to controls. An increase in apoptosis is also seen when p53Scer\UAS.Dp53 is expressed in a p535A-1-4 mutant background.

Mitotic chromosomes from the brains of p535A-1-4/p535A-1-4 third instar larvae treated with radiation show significant increases in the number of breaks per nucleus compared to wild type (radiation sensitive). Wild type larval wing discs show two phases of cell death in response to irradiation: first signs of cell death are clear after 4h and plateau around 8h, with cell death again increasing from 16-24h; irradiated p535A-1-4/p535A-1-4 discs do not show early induction of cell death but do show an elevation between 16-24h.

Homozygous wing discs show little, if any, apoptosis 4 hours after exposure to 4000 rads of X-ray irradiation, in contrast to the high level of apoptosis seen in wild-type discs. At 20 hours after irradiation, apoptosis levels in the mutant discs are comparable to those seen in wild-type discs.

Mutant larvae show greater sensitivity to 0.5 or 1μM maytansinol than wild-type controls.

In contrast to wild-type controls, virtually no apoptotic cells are observed in homozygous p535A-1-4 mutant eye discs after treatment with ionising irradiation.

The presence of p535A-1-4 largely abolishes the apoptotic response 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 using any of DcY-FrTr4B1A, DcYy+, P{FRT(whs)}(8F)105, P{inv.FRT}Dc2-127, P{inv.FRT}Dc2-FrTr1B or P{inv.FRT}Dc3-FrTr1D. Wing disc apoptosis is also suppressed 12-14 hours after heat shock, and this can be seen using any of DcY-FrTr4B1A, DcYy+, DcY-H1, DcY-H2, DcY-H3, P{FRT(whs)}(8F)105, P{inv.FRT}Dc2-127, P{inv.FRT}Dc2-FrTr1B 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. Some cell death is still observed when dicentrics are generated using DcYy+. When dicentrics are generated in larval neuroblast cells, fewer than 40% of p535A-1-4 mutant larval neuroblast cells have normal karyotypes 96 hours after heat shock of P{inv.FRT}Dc2-FrTr1B or P{FRT(whs)}(8F)105, whereas 80-90% appear normal in the dicentric controls. Phenotypes observed in cells with abnormal karyotypes include the presence of multiple acentric chromatids, chromosome fusions and tetraploidy.

Programmed cell death of primordial germ cells (PGCs), which is essentially complete by stage 12 of embryogenesis in wild type, is disrupted in mutant embryos; the total average number of PGCs is normal in the mutants at stage 10, but although there is a gradual reduction in the number of PGCs, it is decreased compared to wild type, such that at stage 14 the average number of PGCs is higher in the mutant embryos compared to wild type.

The average number of PGCs per embryo in p535A-1-4/Dp(3;3)p53-ns mutants is similar to wild type at stage 10, but by stage 14 the average number of PGCs in the mutant embryo is significantly higher than in wild type, as programmed cell is defective in the mutant embryos.

Although PGCs are able to incorporate into the gonad in p535A-1-4 embryos, an average of 9.1 germ cells ectopic to the gonad are seen at stage 14 (compared to the wild-type average of 0.4 ectopic germ cells at this stage).

Although PGCs are able to incorporate into the gonad in p535A-1-4/Dp(3;3)p53-ns embryos, an average of 6.5 germ cells ectopic to the gonad are seen at stage 14 (compared to the wild-type average of 0.4 ectopic germ cells at this stage).

Mutant third instar larvae show a dramatic reduction in survival after irradiation with 2krad X rays compared to control larvae.

p535A-1-4 mutants display a reduction in radiation-induced cell death, with only approximately 50% eclosing after irradiation with 4,000R.

p535A-1-4 flies do not show age-dependent degeneration of rhabdomeres or photoreceptor cells.

Homozygous mutant animals have compromised viability, with 83.3% of third instar larvae eclosing to adults (compared to 98.1% in wild-type). These mutants show a consistent, fully penetrant lack of cell death at times it is readily detectable in other backgrounds. When irradiated, 71% of animals eclose into adults.

No apoptosis is observed in response to irradiation in mutant third instar wing disc (in contrast to wild-type discs, which show an increase in apoptosis after irradiation).

Shows no obvious phenotype.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
NOT Enhanced by
Statement
Reference
Suppressed by
NOT suppressed by
Enhancer of
NOT Enhancer of
Statement
Reference
Suppressor of
NOT Suppressor of
Statement
Reference

p535A-1-4/p53[+] is a non-suppressor of melanotic necrosis | pupal stage P5 phenotype of Pfas1-6

p535A-1-4 is a non-suppressor of increased cell death phenotype of Rbf120a

p535A-1-4 is a non-suppressor of visible phenotype of upd1GMR.PB

Other
Phenotype Manifest In
NOT suppressed by
Statement
Reference
Enhancer of
Statement
Reference

p535A-1-4/p535A-1-4 is an enhancer of female germline stem cell | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

p535A-1-4/p53[+] is an enhancer of wing phenotype of N55e11

p535A-1-4/p53[+] is an enhancer of wing phenotype of wg1

NOT Enhancer of
Statement
Reference
Suppressor of
Statement
Reference

p535A-1-4/p53[+] is a suppressor of female germline stem cell | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

p535A-1-4 is a suppressor of eye phenotype of hidGMR.PG

p535A-1-4 is a suppressor of eye disc phenotype of Rbf120a

p535A-1-4/p535A-1-4 is a suppressor of eye phenotype of E(mus304)[+]/DNApol-α180Emus304, mei-4129D

NOT Suppressor of
Other
Additional Comments
Genetic Interactions
Statement
Reference

p535A-1-4 homozygosity does not suppress the apoptosis in the third instar larval wing disc dorsal compartment induced by the expression of pnutGD1512 from the second instar larval stage under the combined control of Scer\GAL4ap-md544 and Gal80[ts].

p535A-1-4 is epistatic to Corp95B in the BARTL (Bar and Telomere Loss) assay; double mutant flies have almost wild-type eyes in this assay, indicating suppression of the eye ablation phenotype resulting from an irreparable DNA double-stranded break, as occurs in p535A-1-4 single mutants.

p535A-1-4 suppresses the increase in irradiation-induced apoptosis seen in Corp95B mutant flies, with the double mutant phenotype being indistinguishable from that of p535A-1-4 single mutants.

p535A-1-4 suppresses the reduced eye phenotypes caused by expression of hidGMR.PG.

The apoptosis that occurs at the interface of wild type and M(2)56FH/+ cells in M(2)56FH/+ wing discs in which wild type clones have been induced is not significantly lowered in discs that are also mutant for p5311-1B-1/p535A-1-4.

Presence of p535A-1-4/p535A-1-4 suppresses heart structural defects seen in Scer\GAL4tin.CΔ4>ScoxGD898 flies: there are no obvious morphological heart defects (including correct alignment of cardiomyocyte myofibrils).

p535A-1-4/p535A-1-4 does not suppress increased cell death seen in Ipk220B/Ipk220B third instar larval wing discs.

One copy of p535A-1-4 does not suppress the eye roughness seen when SRm160GE25979 is expressed under the control of Scer\GAL4GMR.PU.

p535A-1-4/p5311-1B-1 partially suppresses the neuroblast loss seen in Fen1EY12786 mutant larval brains.

Clbn1Q/Clbn1Q p535A-1-4/p535A-1-4 double mutants show the same degree of radiation sensitivity (increase in the number of breaks per nucleus in mitotic chromosomes in third instar larval brains compared to wild type) as Clbn1Q/Clbn1Q or p535A-1-4/p535A-1-4 mutants alone. Clbn1Q/Clbn1Q p535A-1-4/p535A-1-4 double mutant third instar larval wing discs appear to have almost a complete block of cell death (apoptosis) in response to irradiation. p535A-1-4/p535A-1-4 significantly enhances melanotic tumor formation in tefustg/tefustg third instar larvae (29.5%).

p535A-1-4/+ does not suppress the necrosis seen in stage P5 ade21-6 pupae.

Homozygosity for p535A-1-4 in the Scer\GAL4ey.PU, vitoGD10890 background does not rescue the increased apoptosis phenotype or eye disc size.

A loss of heterozygosity assay, using mwh1 as a marker, reveals that a Su(var)2-1003697, lwr05486, or smt3k06307 heterozygous background increases the number of mwh1 clones after irradiation with 250 rad of X-rays, in p535A-1-4 mutants.

p535A-1-4 partially suppresses the increased levels of apoptosis seen in mitotically cycling wing disc cells and ovarian follicle cells following expression of duphsp70.T:Hsap\MYC.

The increased apoptosis that is seen in wing discs expressing dmScer\UAS.cZa under the control of Scer\GAL4ap-md544 is not reduced by p535A-1-4/p5311-1B-1.

The apoptosis in the eye disc induced by the co-expression of E2fScer\UAS.cNa and DpScer\UAS.cDa under the control of Scer\GAL4GMR.PF is unaffected by homozygous p535A-1-4.

The wave of apoptosis that appears in the absence of irradiation in Rbf120a mutant eye discs is unaffected by p535A-1-4.

The elevated level of DNA-damage induced apoptosis in Rbf120a mutant eye discs is suppressed by p535A-1-4.

p535A-1-4/p535A-1-4 completely suppresses the rough eye phenotype of DNApol-α180Emus304/+ ; mei-4129D/Y flies. The increased level of apoptosis seen in DNApol-α180Emus304/+ ; mei-4129D/Y wing discs is restored by p535A-1-4/p535A-1-4 to the level seen in mei-4129D/Y single mutants.

The cell cycle arrest and undergrowth phenotype of 96 hour wing discs with Scer\GAL4hh-Gal4>WScer\UAS.cYa, BacA\p35Scer\UAS.cHa cells in the posterior is completely alleviated in a p535A-1-4 background.

While 59% of Scer\GAL4Act5C.PI>wgScer\UAS.cLa prothoracic leg discs form a blastema, only 22% of Scer\GAL4Act5C.PI>wgScer\UAS.cLa, p535A-1-4 legs form a blastema.

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).

p535A-1-4 Ada2b2 double mutant third instar wing discs show a small amount of apoptosis in the absence of irradiation, but there is no increase in apoptosis in these discs following irradiation.

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 slightly alleviated by combination with a single copy of p535A-1-4 but is actually made worse by p535A-1-4 homozygosity.

p535A-1-4 enhances the neurodegeneration phenotype induced by expression of Scer\GAL4elav.PLu>Hsap\MAPTR406W.Scer\UAS.

Expression of BacA\p35GMR.PH in either wild-type or p535A-1-4 mutant cell clones does not affect clonal growth in controls.

Preventing apoptosis, through the presence of BacA\p35GMR.PH, allows p535A-1-4, dmαTub84B.PBb mutant clones to grow to the same size, and at the same rate, as dmαTub84B.PBb-expressing super-competitor clones. Thus, the inability of the p535A-1-4, dmαTub84B.PBb super-competitor population to expand is due to cell death that requires the presence of nearby wild-type cells.

p535A-1-4/p535A-1-4 significantly partially suppresses age-dependent degeneration of rhabdomeres and photoreceptor cells in Hsap\HTTGMR.Q120 flies.

Complementation and Rescue Data
Not rescued by
Comments

Expression of p53+tTa rescues the partial suppression of apoptosis seen in p535A-1-4 mutant cells containing dicentric chromosomes (generated using Scer\FLP1hs.PP-induced recombination in chromosomes containing inverted Scer\FRT sites).

Images (0)
Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer
Comments
Comments

Generated in screen described in FBrf0149003.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (17)
References (52)