The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity

Fogarty, Patrick F.; Campbell, Shelagh D.; Abu-Shumays, Robin; Phalle, Brigitte de Saint; Yu, Kristina R.; Uy, Brian; Goldberg, Michael L.; Sullivan, William M.

doi:10.1016/s0960-9822(06)00189-8

Cited by 205 publications

(186 citation statements)

References 31 publications

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“…We conclude that grp is essential for the DNA replication checkpoints in cellular stage embryos, whereas the DNA damage checkpoint requires little to no Grp. This conclusion agrees well with roles for Grp earlier in embryogenesis; Grp is required for a replication checkpoint in syncytial stage embryos, but not when DNA is damaged by irradiation (Fogarty et al, 1997;Sibon et al, 1997;Takada et al, 2003). Grp plays a redundant role with Chk2 to regulate the entry into mitosis after DNA damage checkpoint in the larvae (Brodsky et al, 2004).…”

Section: Metaphase-anaphase Checkpointsupporting

confidence: 84%

“…Grp protein, similar to transcript expression, is present in newly deposited embryos and is at the highest levels during 2-8 hours AED, which loosely corresponds to cellular cycles 14-16 (Fogarty et al, 1997) (Fig. 5A).…”

Section: Grp 1 Mutants Can Regulate Mitosis After Irradiationmentioning

confidence: 99%

“…All mutant alleles used here, mei-41 D12 , grp 1 , bubR1 KO3110 , dup a1 and dup a3 , have been described before (Fogarty et al, 1997;Laurencon et al, 2003;Whittaker et al, 2000). Fly stocks carrying Histone H2Av-GFP transgene has also been described previously (Clarkson and Saint, 1999).…”

Section: Fly Stocksmentioning

confidence: 99%

“…Thus, regulation of the cell cycle by checkpoints can drastically change during development. Drosophila Chk1, encoded by grp, along with the ATR homolog, mei-41, are required to delay the entry into mitosis when DNA replication is incomplete during syncytial cycles (Fogarty et al, 1997;Sibon et al, 1999) (Table 1). Neither grp nor mei-41, however, is needed for DNA damage responses in syncytial cycles (Sibon et al, 2000) (Table 1).…”

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confidence: 99%

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Regulation of mitosis in response to damaged or incompletely replicated DNA require different levels of Grapes (DrosophilaChk1)

Purdy

Uyetake

Cordeiro

et al. 2005

Journal of Cell Science

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Checkpoints monitor the state of DNA and can delay or arrest the cell cycle at multiple points including G1-S transition, progress through S phase and G2-M transition. Regulation of progress through mitosis, specifically at the metaphase-anaphase transition, occurs after exposure to ionizing radiation (IR) in Drosophila and budding yeast, but has not been conclusively demonstrated in mammals. Here we report that regulation of metaphase-anaphase transition in Drosophila depends on the magnitude of radiation dose and time in the cell cycle at which radiation is applied, which may explain the apparent differences among experimental systems and offer an explanation as to why this regulation has not been seen in mammalian cells. We further document that mutants in Drosophila Chk1 (Grapes) that are capable of delaying the progress through mitosis in response to IR are incapable of delaying progress through mitosis when DNA synthesis is blocked by mutations in an essential replication factor encoded by double park (Drosophila Cdt1). We conclude that DNA damage and replication checkpoints operating in the same cell cycle at the same developmental stage in Drosophila can exhibit differential requirements for the Chk1 homolog. The converse situation exists in fission yeast where loss of Chk1 is more detrimental to the DNA damage checkpoint than to the DNA replication checkpoint. It remains to be seen which of these two different uses of Chk1 homologs are conserved in mammals. Finally, our results demonstrate that Drosophila provides a unique opportunity to study the regulation of the entry into, and progress through, mitosis by DNA structure checkpoints in metazoa.

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Section: Metaphase-anaphase Checkpointsupporting

confidence: 84%

Section: Grp 1 Mutants Can Regulate Mitosis After Irradiationmentioning

confidence: 99%

Section: Fly Stocksmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of mitosis in response to damaged or incompletely replicated DNA require different levels of Grapes (DrosophilaChk1)

Purdy

Uyetake

Cordeiro

et al. 2005

Journal of Cell Science

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“…The differences in timing were recently shown to depend in part on the widely conserved DNA replication checkpoint, which can delay progression through S phase in response to defects in DNA replication in early embryonic cells (Brauchle et al, 2003). Similarly in Drosophila, a DNA replication/damage checkpoint regulated by grapes and Mei-41/ATM has been found to operate during late syncytial embryonic divisions to ensure proper DNA replication before entry into mitosis (Fogarty et al, 1997;Sibon et al, 1999). In contrast to S phase, the duration of mitosis is roughly constant in different early C. elegans embryonic cells (Edgar and McGhee, 1988;Encalada et al, 2000), suggesting that the differential control of mitotic progression by the spindle checkpoint does not contribute to the asynchrony of early embryonic cell cycles.…”

Section: Differential Control Of Cell Division Timing In Early Embryosmentioning

confidence: 99%

A Spindle Checkpoint Functions during Mitosis in the EarlyCaenorhabditis elegansEmbryo

Encalada

Willis

Lyczak

et al. 2005

MBoC

118

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During mitosis, chromosome segregation is regulated by a spindle checkpoint mechanism. This checkpoint delays anaphase until all kinetochores are captured by microtubules from both spindle poles, chromosomes congress to the metaphase plate, and the tension between kinetochores and their attached microtubules is properly sensed. Although the spindle checkpoint can be activated in many different cell types, the role of this regulatory mechanism in rapidly dividing embryonic animal cells has remained controversial. Here, using time-lapse imaging of live embryonic cells, we show that chemical or mutational disruption of the mitotic spindle in early Caenorhabditis elegans embryos delays progression through mitosis. By reducing the function of conserved checkpoint genes in mutant embryos with defective mitotic spindles, we show that these delays require the spindle checkpoint. In the absence of a functional checkpoint, more severe defects in chromosome segregation are observed in mutants with abnormal mitotic spindles. We also show that the conserved kinesin CeMCAK, the CENP-F-related proteins HCP-1 and HCP-2, and the core kinetochore protein CeCENP-C all are required for this checkpoint. Our analysis indicates that spindle checkpoint mechanisms are functional in the rapidly dividing cells of an early animal embryo and that this checkpoint can prevent chromosome segregation defects during mitosis. INTRODUCTIONDuring mitosis, some microtubules emanating from bipolar microtubule organizing centers grow toward chromosomes and attach to specialized chromosomal regions called kinetochores (Skibbens and Hieter, 1998;Cleveland et al., 2003). Once captured, sister chromatids are segregated, one to each of two daughter cells. Eukaryotic cells have evolved a mechanism called the spindle checkpoint, to monitor chromosomal segregation and increase the fidelity of mitosis (reviewed in Gardner and Burke, 2000;McIntosh et al., 2002). Until spindle microtubules from both poles capture and align all sister chromatid pairs at a metaphase plate, the spindle checkpoint produces a delay in the onset of anaphase. If this delay is bypassed by reducing checkpoint function, anaphase starts prematurely, and daughter cells may receive unequal complements of chromosomes. Such genomic instability can result in lethality and in tumorigenesis (Hartwell and Kastan, 1994;Basu et al., 1999).Originally identified and characterized in Saccharomyces cerevisiae, seven spindle assembly checkpoint genes (MAD1, MAD2, MAD3, BUB1, BUB2, BUB3, and MPS1) are known to function at kinetochores to inhibit anaphase onset, or to mediate mitotic exit in the presence of spindle abnormalities (Hoyt et al., 1991;Li and Murray, 1991). Mutations in these genes reduce or eliminate the cell cycle delays that normally occur after treatment with microtubule depolymerizing drugs (Wang and Burke, 1995;Pangilinan and Spencer, 1996). Bub1 and Bub3 form a protein kinase complex that, in concert with Mps1, functions at kinetochores upstream of Mad1 and Mad2 (Roberts et al., 1994;H...

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Blastoderm Formation and Cellularisation inDrosophila melanogaster

Kotadia

Crest

Tram

et al. 2010

Encyclopedia of Life Sciences

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Immediately following fertilisation in Drosophila and many other arthropods, the embryo undergoes a series of rapid syncytial nuclear divisions. These divisions are driven by maternally supplied components and occur in the absence of zygotic transcription. Unlike typical cell divisions, these divisions alternate between S and M phases, resulting in cell cycles that last only from 10 to 25 min. After four rounds of division, the nuclei undergo axial expansion, a process that relies on microfilaments. Subsequently migration of the nuclei to the cortex relies on microtubules. Once at the cortex, the nuclear divisions occur on a single plane and rely on partial cleavage furrows to maintain an even distribution. The cortical nuclear divisions continue until the mid‐blastula transition (MBT), at which time cellularisation results in the formation of a multicellular embryo. Key Concepts: Fertilisation triggers a series of events that induces the first mitotic cycle, a gonomeric division between the male and female pronucleus. After fertilisation, the embryo undergoes 13 synchronous divisions within a syncytium. Divisions 10–13 occur at the cortex of the embryo and require reorganisation of actin and membrane into metaphase furrows. At cycle 14, the cell cycle pauses and cellularisation occurs forming individual somatic cells. Cellularisation, a key feature of the mid‐blastula transition, marks the time at which zygotic transcription occurs and maternal products are degraded.

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The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity

Cited by 205 publications

References 31 publications

Regulation of mitosis in response to damaged or incompletely replicated DNA require different levels of Grapes (DrosophilaChk1)

Regulation of mitosis in response to damaged or incompletely replicated DNA require different levels of Grapes (DrosophilaChk1)

A Spindle Checkpoint Functions during Mitosis in the EarlyCaenorhabditis elegansEmbryo

Blastoderm Formation and Cellularisation inDrosophila melanogaster

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