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General Information
Symbol
Dmel\mei-41D3
Species
D. melanogaster
Name
FlyBase ID
FBal0012154
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
mei41D3
Key Links
Allele class
Mutagen
    Nature of the Allele
    Allele class
    Mutagen
    Mutations Mapped to the Genome
     
    Type
    Location
    Additional Notes
    References
    Nucleotide change:

    C16393759T

    Reported nucleotide change:

    T3768A

    Amino acid change:

    A647V | mei-41-PA

    Reported amino acid change:

    A384V

    Comment:

    Position of mutation on reference sequence inferred by FlyBase curator. Reported nucleotide change is not consistent with amino acid change.

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

    Amino acid replacement: A384V.

    In addition to the A384V amino acid replacement, which may cause the mutant phenotype, a number of additional amino acid changes are present compared to the U34925 mei-41 GenBank sequence (these "common" mutations are also present in other mei-41 mutant alleles, possibly due to variability present in the mutagenised population).

    Nucleotide substitution: T3768A.

    Nonsense mutation at codon 42, resulting in a stop six codons later.

    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 ( 0 )
    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

    mei-41D3 null embryos prematurely undergo mitosis 13; cycle 14 nuclei are defective, with massive chromosome bridging.

    mei-41D3 mutants exhibit an accumulation of γHis2Av foci that persist through meiotic prophase, corresponding to unrepaired meiotic double-strand breaks. A mean of 21 γ-His2Av foci is present in spn-A1 region 3 oocytes, which is similar to estimates for the total number of double strand breaks per nucleus.

    Homozygous females show a high frequency (73%) of region 3 cysts with two pro-oocytes (as assayed by c(3)G staining) compared to a frequency of only 9.5% in wild type.

    Irradiation of mei-41D3 mutants with 4000 rad does not arrest cell division.

    Eggs laid by mei-41D3 females have the correct number of dorsal appendages.

    The S-phase index is increased 2.4-fold in mei-41D3 double mutants compared to wild-type.

    mei-41D3 mutant wing discs fail to arrest in response to a range of irradiation doses.

    mei-41D3 mutant cells exhibit DNA breaks and telomere fusions in metaphase and anaphase at almost the same level as wild-type cells.

    Mutant eyes (generated using the "EGUF" system) do not display morphological defects when larvae are raised on media containing 2 mmol caffeine/L and 3 mmol hydroxyurea/L.

    Heterozygotes are sensitive to methyl methanesulfonate compared to wild-type animals. Hemizygous larvae show 98% loss of the G2/M checkpoint (this number is the average number of mitotic cells per eye disc after exposure of male hemizygous larvae to 500R of X rays expressed as a percentage of the number of mitotic cells per eye disc before irradiation, wild-type values range from 5 to 15%).

    No precocious anaphases are seen in mutant oocyte nuclei.

    Homozygous females produce cellularised embryos at a very low frequency (2%).

    Defects are seen during mitosis 13 and 14 in embryos derived from homozygous females mated to wild-type males. Anastral spindles with broad poles and numerous free cytoplasmic microtubules are seen.

    Homozygous females are sterile and produce eggs that do not hatch. Most of the embryos derived from these eggs develop to the syncytial blastoderm stage and have relatively normal nuclear morphology up to division 12 or 13. Later embryos show significant variability in nuclear size and distribution. The embryos fail to cellularise after mitosis 13 and proceed through at least two additional syncytial cycles of spindle assembly and disassembly. The lengths of interphase and mitosis are close to wild type until division 11, however, during divisions 12 and 13 interphase is significantly shorter than in wild-type embryos. Embryos derived from homozygous females do not delay nuclear envelope breakdown in response to aphidicolin treatment, in contrast to wild-type embryos. Homozygotes are more sensitive to hydroxyurea and methyl methanesulfonate than wild-type. Approximately 4% of embryos derived from mei-41D3/mei-41D5 females hatch at 25oC, while approximately 45% hatch at 20oC.

    Mutant larvae die on exposure to MMS. Homozygous females are sterile.

    Defect in a cell cycle checkpoint so that cells with damaged DNA (for example by X ray) are allowed to enter mitotic metaphase.

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

    mei-41D3/mei-41D3 is an enhancer of decreased cell number | female | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

    mei-41[+]/mei-41D3 is an enhancer of decreased cell number | female | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

    Suppressor of
    Statement
    Reference
    NOT Suppressor of
    Statement
    Reference
    Other
    Phenotype Manifest In
    Suppressed by
    Statement
    Reference

    mei-41D3 has phenotype, suppressible | partially by Wee1+tPa

    Enhancer of
    Statement
    Reference

    mei-41[+]/mei-41D3 is an enhancer of female germline stem cell | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

    mei-41D3/mei-41D3 is an enhancer of female germline stem cell | adult stage | temperature conditional phenotype of Crei\I-CreIhs.PR

    mei-41[+]/mei-41D3 is an enhancer | maternal effect of phenotype of Wee1DS1

    mei-41D3/mei-41D3 is an enhancer | maternal effect of phenotype of Wee1DS1

    Suppressor of
    Statement
    Reference

    mei-41D3 is a suppressor of karyosome | heat sensitive phenotype of tefuatm-8

    mei-41D3/mei-41D3 is a suppressor of microtubule organizing center & oocyte phenotype of armi72.1/armi1

    mei-41D3 is a suppressor of karyosome phenotype of spn-D2/spn-D1

    NOT Suppressor of
    Statement
    Reference

    mei-41D3 is a non-suppressor of oocyte | germline clone phenotype of Aatfnutmeg-21.3

    mei-41D3 is a non-suppressor of karyosome phenotype of Brca2KO/Brca256E

    mei-41D3 is a non-suppressor of dorsal appendage phenotype of Brca2KO/Brca256E

    mei-41D3 is a non-suppressor of dorsal appendage phenotype of spn-E1

    mei-41D3 is a non-suppressor of karyosome phenotype of Src64BΔ17

    mei-41D3 is a non-suppressor of karyosome phenotype of encR17

    mei-41D3 is a non-suppressor of egg chorion phenotype of encR17

    Other
    Statement
    Reference

    Df(2R)LL5, mei-41D3, mei-W681 has oocyte nucleus & meiotic cell cycle phenotype

    Additional Comments
    Genetic Interactions
    Statement
    Reference

    mei-41D3 is unable to suppress the early oogenesis arrest and oocyte polarity phenotypes seen in Aatfnutmeg-21.3 mutant germline clones.

    The karyosome morphology defects found in female tefuatm-8 mutants at the restrictive temperature of 25[o]C are suppressed in a mei-41D3 mutant background.

    33% of eggs derived from mei-41D3 ; rhiKG00910/rhi02086 double mutant females have two normal dorsal appendages.

    56% of eggs derived from mei-41D3/mei-41D3 ; armi1/armi72.1 double mutant females have normal dorsal appendages, but the fraction of embryos with normal dorsal appendages increases to 83% if the females are fed caffeine.

    The addition of mei-41D3 results in little or no suppression of the eggshell patterning and karyosome formation defects of Brca2KO/Brca256E females.

    Mutant larvae do not show efficient G2 arrest after exposure to 500Rad or 4000Rad irradiation. The mutant larvae do not show a reduction in BrdU incorporation after a 4000Rad irradiation exposure, in contrast to wild-type larvae.

    The mei-41D3 mutation partially suppresses the fused dorsal appendage phenotype of armi72.1/armi1 eggs; 56% of mei-41D3; armi72.1/armi1 eggs show wild-type appendage morphology.

    The microtubule-organizing center phenotype of armi72.1/armi1 oocytes is partially suppressed by the mei-41D3 mutation.

    The fused dorsal appendage phenotype of spn-E1 eggs is not suppressed by mei-41D3.

    In mei-41D3;pr-set720 double mutants, the mitotic index, significantly reduced in pr-set720 mutants, is rescued to be similar to that observed in wild-type and the homozygous mei-41D3 mutant. The number of prophase cells is reduced compared with the number observed in pr-set720 homozygotes and becomes similar to wild-type and pr-set720 mutants. The ratio of anaphase/telophase cells with lagging chromatids is increased when the DNA damage checkpoint is abolished in the double homozygous mei-41D3;pr-set720 mutant, indicating that the defect in chromomsome condensation is independent of checkpoint activation and that, in the absence of the checkpoint, the severity of the chromosome condensation defect is enhanced.

    tefu1 mei-41D3 double mutant cells exhibit more DNA breaks and telomere fusions in metaphase and anaphase than in wild-type cells.

    The karyosome defects seen in spn-D1/spn-D2 egg chambers are strongly suppressed by mei-41D3.

    mei-41D3/mei-41RT1 partially suppresses the dorsal appendage defects of mus301094 homozygotes; 70% of eggs derived from double mutant females have wild-type dorsal appendages, 21% have fused dorsal appendages and 9% have no dorsal appendages. mei-41D3/mei-41RT1 partially suppresses the dorsal appendage defects of eggs derived from spn-Bunspecified females.

    In mei-41D3; mei-W681/Df(2R)LL5 oocytes most nuclei exhibit either disorganised spindles and multiple chromatin masses or premature anaphases.

    In mei-41D3; mei-W681/Df(2R)LL5 oocyte nuclei most nuclei are either exhibit disorganised spindles and multiple chromatin masses or premature anaphases.

    20% of embryos derived from homozygous mei-41D3 females cellularise if they are carrying one copy of wee+tPa, and 50% cellularise if they are carrying two copies of wee+tPa (and some develop to adulthood in this case). The incompletely penetrant syncytial arrest phenotype of embryos derived from homozygous weeDS1 females is enhanced if the females also carry mei-41D3, so that only 39% of the embryos cellularise if the females carry one copy of mei-41D3 and only 29% of the embryos cellularise if the females carry two copies of mei-41D3.

    The egg shell ventralisation and karyosome defects seen in hemizygous encR17 females are not suppressed by mei-41D3.

    The eggshell patterning defects of eggs derived from spn-BBU/spn-BBU females are suppressed if the females also carry mei-41D3/+ or mei-41D3/mei-41RT1. The eggshell patterning defects of eggs derived from mus301D4/mus301094 females are suppressed if the females also carry mei-41D3/+ or mei-41D3/mei-41D3. The eggshell patterning defects of eggs derived from vasRG53/vasPH165 females are not suppressed if the females also carry mei-41D3/mei-41D3.

    mei-41D3 grpfsA4 double heterozygous larvae are more sensitive to methyl methanesulfonate than single heterozygous larvae. If mei-41D3/mei-41D5 females are also heterozygous for grpfsA4, the hatch rates are reduced to 1% and 23% at 25oC and 20oC respectively. The lethality of embryos derived from mei-41D3/mei-41D5 females is partly rescued if the females are also heterozygous for either CycAunspecified or CycBunspecified, and greater rescue is seen if the females are also heterozygous for both CycAunspecified and CycBunspecified.

    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 further exacerbated by mei-41D3 in homo- or heterozygosity.

    mei-41D3;Crei\I-CreIhs.PR double mutants have fewer GSCs per germarium than wild-type controls even without the induction of DNA damage by heat-shock.

    Complementation and Rescue Data
    Rescued by
    Comments

    Both MMS sensitivity and sterility phenotypes are rescued by mei-41+t10.5.

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

    The recovery of chromosomes undergoing P-element transposition in the presence of P\TΔ2-3 is severely reduced in mei-41D3 flies, suggesting that mei-41+ function is required for the recovery of these chromosomes. This instability is reversed if P\TSal is also present.

    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (2)
    References (38)