Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex in<i>Drosophila melanogaster</i>

Pál, Margit; Nagy, Olga; Ménesi, Dalma; Udvardy, Andor; Deák, Péter

doi:10.1242/jcs.004762

Cited by 29 publications

(27 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of an RNAi construct targeting Cdc16 in imaginal disc cells resulted in a mitotic arrest phenotype (Supplemental Fig. S2), as expected from a knockdown of APC/C function (Deak et al 2003;Pal et al 2007). Expression of the Cdc16-specific UAS-RNAi construct in salivary glands, using ptc-Gal4 in combination with Gal80 ts , was induced at 10-18 h AED to deplete APC/C function after the onset of endoreplication.…”

Section: Depletion Of Apc/c Activity Compromises Endoreplicationmentioning

confidence: 52%

“…Most genes involved in Mphase control (rca1, Cdk1, string/Cdc25, Cyclin A, and Cyclin B) displayed a far stronger reduction (400-to 8000-fold). Importantly, Fzr as well as the two APC/C subunits morula/APC2 (mr) and Cdc16/APC6 (Reed and Orr-Weaver 1997;Kashevsky et al 2002;Pal et al 2007) were expressed at levels similar to those of the S-phase regulators, which are known to be involved in endoreplication. We also compared protein levels of the APC/C activator Fzr in embryonic protein extracts and salivary glands (Fig.…”

Section: Expression Of Mitotic Genes and Fzr In Endoreplicating Cellsmentioning

confidence: 99%

“…To verify that suppression of APC/C activity impairs endoreplication, we depleted Cdc16, a core component of the APC/C (Huang and Raff 2002;Pal et al 2007). Overexpression of an RNAi construct targeting Cdc16 in imaginal disc cells resulted in a mitotic arrest phenotype (Supplemental Fig.…”

Section: Depletion Of Apc/c Activity Compromises Endoreplicationmentioning

confidence: 99%

See 2 more Smart Citations

The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles

Zielke¹,

Querings²,

Rottig

et al. 2008

Genes Dev.

111

View full text Add to dashboard Cite

Endoreplicating cells undergo multiple rounds of DNA replication leading to polyploidy or polyteny. Oscillation of Cyclin E (CycE)-dependent kinase activity is the main driving force in Drosophila endocycles. High levels of CycE-Cdk2 activity trigger S phase, while down-regulation of CycE-Cdk2 activity is crucial to allow licensing of replication origins. In mitotic cells relicensing in S phase is prevented by Geminin. Here we show that Geminin protein oscillates in endoreplicating salivary glands of Drosophila. Geminin levels are high in S phase, but drop once DNA replication has been completed. DNA licensing is coupled to mitosis through the action of the anaphase-promoting complex/cyclosome (APC/C). We demonstrate that, even though endoreplicating cells never enter mitosis, APC/C activity is required in endoreplicating cells to mediate Geminin oscillation. Down-regulation of APC/C activity results in stabilization of Geminin protein and blocks endocycle progression. Geminin is only abundant in cells with high CycE-Cdk2 activity, suggesting that APC/C-Fzr activity is periodically inhibited by CycE-Cdk2, to prevent relicensing in S-phase cells.[Keywords: Anaphase-promoting complex; cell cycle; DNA licensing; Drosophila; endoreplication] Supplemental material is available at http://www.genesdev.org. The precise duplication of the genome is crucial for the survival of any organism. In multicellular organisms genome instability potentially gives rise to cancer and thus compromises the life of the whole organism. To maintain the integrity of the genome, DNA replication, and mitosis must be coordinated during cell division cycles so that DNA replication occurs only once per cycle and mitosis only after complete duplication of the genome. To avoid rereplication events, a network of proteins ensures that cells acquire the license for DNA replication only in a specific phase of the cell cycle. DNA licensing involves the formation of prereplication complexes (pre-RC), which can only assemble during late mitosis and G1 (for review, see Bell and Dutta 2002;Blow and Dutta 2005). Pre-RC assembly on replication origins involves a variety of conserved components including the ORC1-6 complex, Cdc6, Cdt1/Double-parked, and the MCM2-7 helicase. Once MCM2-7 proteins are loaded onto the DNA, licensing is completed and the replication origins are ready for firing (for review, see Bell and Dutta 2002;Blow and Dutta 2005).Several mechanisms ensure that replication origins are fired only once during a cell cycle (for review, see Machida et al. 2005). Of particular importance is the temporal separation of pre-RC formation and origin firing. Pre-RC assembly occurs only in G1 because it depends on low Cdk activity while high Cdk activity is required for origin firing. The increase in Cdk activity at the G1-S transition does not only trigger origin firing, but at the same time also results in phosphorylation of several pre-RC components (ORC, Cdc6, Cdt1,. These modifications are thought to prevent reassembly of these components into pre-R...

show abstract

Section: Depletion Of Apc/c Activity Compromises Endoreplicationmentioning

confidence: 52%

Section: Expression Of Mitotic Genes and Fzr In Endoreplicating Cellsmentioning

confidence: 99%

See 1 more Smart Citation

The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles

Zielke¹,

Querings²,

Rottig

et al. 2008

Genes Dev.

111

View full text Add to dashboard Cite

show abstract

“…RNAi and Apc8 RNAi lines have been described previously (Pal et al, 2007). To generate the UAS-Apc10…”

Section: Generation Of Transgenic Fliesmentioning

confidence: 99%

“…2A). In our studies we used RNAi constructs against Apc6/Cdc16 and Apc8 (Pal et al, 2007) and Apc10. Apc6 and Apc8 are tetratrico peptide repeat (TPR) subunits, which, in humans, are part of the core APC/C complex (Vodermaier et al, 2003).…”

Section: Apc/cmentioning

confidence: 99%

APC/CFzr/Cdh1 promotes cell cycle progression during theDrosophilaendocycle

et al. 2008

View full text Add to dashboard Cite

The endocycle is a commonly observed variant cell cycle in which cells undergo repeated rounds of DNA replication with no intervening mitosis. How the cell cycle machinery is modified to transform a mitotic cycle into endocycle has long been a matter of interest. In both plants and animals, the transition from the mitotic cycle to the endocycle requires Fzr/Cdh1, a positive regulator of the Anaphase-Promoting Complex/Cyclosome (APC/C). However, because many of its targets are transcriptionally downregulated upon entry into the endocycle, it remains unclear whether the APC/C functions beyond the mitotic/endocycle boundary. Here, we report that APC/CFzr/Cdh1 activity is required to promote the G/S oscillation of the Drosophila endocycle. We demonstrate that compromising APC/C activity, after cells have entered the endocycle, inhibits DNA replication and results in the accumulation of multiple APC/C targets, including the mitotic cyclins and Geminin. Notably, our data suggest that the activity of APC/CFzr/Cdh1 during the endocycle is not continuous but is cyclic,as demonstrated by the APC/C-dependent oscillation of the pre-replication complex component Orc1. Taken together, our data suggest a model in which the cyclic activity of APC/CFzr/Cdh1 during the Drosophilaendocycle is driven by the periodic inhibition of Fzr/Cdh1 by Cyclin E/Cdk2. We propose that, as is observed in mitotic cycles, during endocycles,APC/CFzr/Cdh1 functions to reduce the levels of the mitotic cyclins and Geminin in order to facilitate the relicensing of DNA replication origins and cell cycle progression.

show abstract

GAL4 induces transcriptionally active puff in the absence of dSAGA- and ATAC-specific chromatin acetylation in the Drosophila melanogaster polytene chromosome

et al. 2009

View full text Add to dashboard Cite

Puffs in the polytene chromosome of Drosophila melanogaster are characteristic of sites of high-level active transcription which can be observed directly under the microscope. We studied the dependence of puff formation on chromatin modifications at a site where a GAL4-inducible transgene is located in the 61C7 cytological region. Immunostaining of salivary gland polytene chromosomes indicated no increase of either dSAGA-specific histone H3 lysine 14, or ATAC-specific histone H4 lysine 5 and 12 acetylation in the puffed region. Nor did we observe increased levels of H4K8ac, H3K18ac, or H4K16ac in the puff. In accordance with the above, puff formation as well as localization of Pol II and GAL4 was detectable at the 61C region in dAda2b and dAda2a null homozygotes, which are dSAGA- and ATAC-specific mutants, respectively. Moreover, the reduced level of JIL-1-specific H3 serine 10 phosphorylation did not abolish puff formation in ATAC mutants. Surprisingly, in wild-type animals dADA3 and GCN5 shared constituents of dSAGA and ATAC, as well as JIL-1 localized specifically to the puff, where the JIL-1-phosphorylated H3S10ph level was also high. Altogether these data strongly suggest that the GAL4 activator can induce transcription and chromatin reorganization seen as a puff without dSAGA- and ATAC-specific histone acetylation and JIL-1-specific histone H3 phosphorylation.

show abstract

Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex inDrosophila melanogaster

Cited by 29 publications

References 33 publications

The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles

The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles

APC/CFzr/Cdh1 promotes cell cycle progression during theDrosophilaendocycle

GAL4 induces transcriptionally active puff in the absence of dSAGA- and ATAC-specific chromatin acetylation in the Drosophila melanogaster polytene chromosome

Contact Info

Product

Resources

About