No mutations have been found in the coding sequence.
mus308D2/Df(3R)Exel6166 larvae are unable to survive exposure to 0.005% mechlorethamine (nitrogen mustard).
mus308D2/Df(3R)Exel6166 animals are able to survive exposures of as high as 4000rads of ionising radiation.
Studies of excision and repair events of P{hswa} in mus308D2/mus308Sz29 males indicate that DNA repair synthesis during synthesis-dependent strand annealing (SDSA) is unaffected in the mutants but that the mutants are defective in end-joining repair of DNA double-strand breaks. There is a substantial increase in the percentage of deletion-associated repair events isolated from mus308D2 mutant males relative to those isolated from wild-type males.
mus308D2 mutants have a similar frequency of single-strand annealing repair (SSA) compared to controls in a P{wIw.FRT} hemizygous assay to study DNA double-stranded break repair when assayed at 32oC or 38oC.
Excision repair capacity is normal and post-replication repair capacity is deficient.
A partial deficiency in the excision repair of pyrimidine dimers originally observed in this mutant is now attributed to the presence of a secondary phr mutation, phrmus308-D2.
Adult survivors of sub-lethal nitrogen mustard treatments exhibit an incompletely penetrant held up wing phenotype, with reduced flight ability. Viability of untreated embryos is reduced, and chromatin organization in inviable embryos is abnormal.
Mutations exhibit a partial deficiency in the capacity to excise UV-induced pyrimidine dimers. In addition cells show defective post-replicative repair of UV damage.
Survival of homozygous larvae is hypersensitive to nitrogen mustard, diepoxybutane and cis-platinum, but not to methyl methanesulfonate. Larval survival is also sensitive to UV treatment and trimethylpsoralen feeding when applied together.
Flies are moderately sensitive to X rays.
Flies exposed to nitrogen mustard show an increase in mitochondrial abnormalities compared to wild-type.
Cells derived from homozygous embryos synthesise DNA at a reduced rate both from an undamaged template and after UV irradiation compared to wild-type cells. Homozygous larval brain ganglia have a reduced ability to synthesise DNA from an undamaged template compared to wild-type.
Sensitive to 0.002% HN2. Not sensitive to 0.125% methyl methanesulfonate.
PolQD5/PolQD2, spn-A093A/spn-A3 has partially lethal phenotype
There is a decrease in the percentage of end-joining repair products in studies of excision and repair events of P{hswa} in spn-A3 mus308D2/spn-A3 mus308ZIII-2003 and spn-A3 mus308D2/spn-A3 mus308D2 double mutant males compared to the percentage seen in spn-A single mutants. The double mutants show a substantial increase in the percentage of deletion-associated repair events isolated compared to controls, as occurs in mus308 single mutants. These males show increased sterility.
spn-A3 mus308D2/spn-A3 mus308ZIII-2003 double mutant males in which excision of P{hswa} is occurring show morphological defects such as abdominal cuticle mispatterning.
mus308D2/mus308D4 has no effect on the frequency of X-Y chromosome nondisjunction seen in Df(1)X-1-53B males, but shows a significant enhancement of meiotic drive in these flies compared to controls.
Boyd.
In spite of the hypersensitivity to DNA cross-linking agents, the initial incision step of DNA cross-link repair appears normal in mus308D2 homozygotes.
Studies of Nuc3 activity in mus308D2 mutants support the hypothesis that the mus308 locus is not the structural gene for Nuc3, but is involved in modifying the pI of the Nuc3 enzyme.