Disease relevance of dap

• Our data indicate that it is through the differential regulation of the cki Dacapo that two modes of cell-cycle regulation are independently maintained within the common cytoplasm of ovarian cysts [1].
• Drosophila S2* cells, but not adult flies, responded to Lys-type Micrococcus luteus PGN, but with significantly less potency compared to Dap-type Escherichia coli PGN, while intact Lys-type PGN from Staphylococcus aureus was inactive [2].

High impact information on dap

• This homeostatic mechanism coordinates rates of G1-->S and G2-->M progression, maintaining normal rates of proliferation when cell cycle controls are perturbed (e.g., by ectopic Dacapo, dWee1, dMyc, or Rheb) [3].
• Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development [4].
• Thus, dap functions during embryogenesis to achieve a precisely timed exit from the cell cycle [5].
• Unlike mammalian cdk inhibitors studied to date, dap is essential for normal embryonic development [5].
• We propose that cyclin E, inhibited by Dacapo in M16, promotes chromosome binding of MCMs [6].

Biological context of dap

• In contrast to the earlier mitoses, mitosis 16 (M16) is followed by G1, and MCMs do not reassociate with chromatin at the end of M16. dacapo mutant embryos lack an inhibitor of cyclin E, do not enter G1 quiescence after M16, and show mitotic reassociation of MCM proteins [6].
• The majority of the EMS-induced mutations that we have identified fall into four complementation groups corresponding to the genes split ends, dacapo, dE2F1, and Cdk2(Cdc2c) [7].
• We also detected a dap-induced sd up-regulation that disrupts wing growth [8].
• This feature is due to the expression of Cyclin E that precedes each cell division, and the differential expression of the S-transition negative regulator, Dacapo [9].
• The dacapo regulatory region includes many independent cis-regulatory elements [10].

Anatomical context of dap

• All retinal cells, including the postmitotic photoreceptor neurons, continue dividing when rbf and dacapo are mutated simultaneously [11].
• We demonstrate a role for the p21(CIP)/p27(Kip1)/p57(Kip2)-like cyclin-dependent kinase inhibitor (cki) dacapo in the maintenance of the meiotic cycle in Drosophila oocytes [1].
• The pan-neural bHLH proteins DEADPAN and ASENSE regulate mitotic activity and cdk inhibitor dacapo expression in the Drosophila larval optic lobes [12].
• On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint [13].

Regulatory relationships of dap

• Our results argue for a mechanism where Cyclin E/Cdk activity induces Dacapo expression but only within certain windows that are permissive for dacapo expression [14].

Other interactions of dap

• The initiation of G1(17) arrest requires the developmentally-induced expression of Dacapo, a p27-like Cyclin E-Cdk2 inhibitor [15].
• Furthermore, we identified pan-neural Prospero as a regulator of dap transcription in the developing nervous system, providing an example how tissue-specific developmental programs can be linked to cell cycle progression [16].
• Notch activity leads to downregulation of String and Dacapo, and activation of Fzr [17].
• We investigated the role of the VG-SD dimer in proliferation and showed that vg antagonizes the effect of dacapo, the cyclin-cdk inhibitor [18].
• Dacapo or tribbles transgene expression arrests cells in either G2 or G2, respectively [19].

References