G12V | Ras85D-PA
Analogous to oncogenic mutations in one of three human RAS genes; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator based on reported amino acid change.
This somatic variant has been found associated with cancer in each of the three paralogous genes in human (KRAS, HRAS, NRAS).
Ras85DV12.sev, cnkhs.sev.T:Zzzz\FLAG double mutants have an average of 1.2 R7 cells per ommatidium. Ras85DV12.sev, cnkΔRIM.hs.sev.T:Zzzz\FLAG double mutants have an average of 2.7 R7 cells per ommatidium.
The rough eye phenotype of Ras85DV12.sev flies is dominantly suppressed by Taf6XS-922 and by Df(3L)kto2. The increased number of R7 photoreceptor cells per ommatidium that is seen in Ras85DV12.sev flies is suppressed from 3.1 to 1.5 by Taf6XS-922/+.
All of the ommatidia in flies expressing svpScer\UAS.cKa under the control of Scer\GAL4sca-537.4 lack R7 and R8 photoreceptor cells. The formation of R7 cells is rescued in these flies by expression of Ras85DV12.sev.
The rough eye phenotype is enhanced by PTP-ERXE-3022 and PTP-ERXE-2776. Ectopic expression of PTP-ERhs.sev in the eye completely blocks the Ras85DV12.sev rough eye phenotype even in the presence of PTP-ERXE-3022.
The rough eye phenotype of Ras85DV12.sev is not enhanced by Src42A1.15. The rough eye phenotype of Ras85DV12.sev is enhanced by Src42A15-1, Src42A18-2, Src42A7-4, Df(2R)nap8, Df(2R)nap9, Df(2R)nap1 or In(2R)bwVDe2LCyR. Lethality at the pupal stage is seen in Src42ASu(phl)1-1 Ras85DV12.sev double heterozygotes.
Ras85DV12.sev in combination with sevS11.T:Hsap\MYC results in synthetic lethality. Expression of sevS11.T:Hsap\MYC above a certain level in embryos results in lethality and this lethality is enhanced by co-expression of Ras85DV12.sev. The lethality is sensitive to the expression levels of both sevS11.T:Hsap\MYC and Ras85DV12.sev. The lethality caused by sevS11.T:Hsap\MYC in combination with Ras85DV12.sev is suppressed by Trl62, trxunspecified, Df(2L)JK12, skd2, osa2, mor1, kto1, kis1, kis2, brm1, brm2, Df(3R)red-P52, RpII140AS, RpII15V, SR3-8XS-701, SR3-8S-959, SR3-7XS-17N, SR3-7S-499, Taf1XS-2232, Taf1S-625, Su(Tpl)S-705, Su(Tpl)S-192, Taf4S-466, Taf4XS-793, Taf6XS-922, Sose4G, Ras85De1B, Ras85DE4, rlXS-2275, rlXS-2442, ksrXS-2424, ksrXS-2832, phyl2829, phyl2245, βggt-IS-2554, mamS-176, Df(3R)293γ5, Df(2L)ast2, Df(2R)nap9, Df(2R)pk78c or Df(3L)vin2. The lethality caused by sevS11.T:Hsap\MYC in combination with Ras85DV12.sev is suppressed by l(3)0624006240, l(3)0626506265, l(3)0929109291, Rpd304556, l(3)0514305143, btl00208, btl04727, frc10098, ftz-f103649, eRF105637, l(3)77CDf04521, tws02414, tws06848, l(3)0360803608, l(3)0665806658, osa04539, fray07551, l(3)0582005820, InR05545, pnt04263b, pnt07825, l(3)0307703077, l(3)0470804708, l(3)0674306743 or l(3)0673406734. The lethality caused by sevS11.T:Hsap\MYC in combination with Ras85DV12.sev is suppressed by the l(3)06948 line (l(3)06948a06948a and sr06948b), by the l(3)03745 line (tws03745a and Dl03745b) and by the l(3)04704 line (l(3)04704a04704a and l(3)04704b04704b). The lethality caused by sevS11.T:Hsap\MYC in combination with Ras85DV12.sev is not suppressed by TfIIA-SE32, ash12, Vha5515, Vha5516, mor2, osa1, sls1, skd1, Df(3R)urd, urd2, vtd3, Pc3 or Pc4.
The rough eye and extra R7 cell phenotype is dominantly suppressed by 14-3-3εS-1259 and 14-3-3εS-696 and recessively suppressed by 14-3-3εj2B10. Df(3R)P14 shows no dominant interaction with Ras85DV12.sev. Heterozygosity for 14-3-3ζP2355 does not alter the Ras85DV12.sev phenotype.
Loss of cno+ activity (cno3 or Df(3R)6-7) does not affect overproduction of R7 cells in Ras85DV12.sev flies but loss of pigment cells is more severe and supernumerary cone cells appear (these cone cells are recruited from a pool of retinal precursors that normally develop into pigment cells and from cells to be eliminated by apoptosis). The phl1 mutation completely suppresses the overproduction of cone cells triggered by the Ras85DV12.sev and cno3 interaction.