DNA-replication checkpoint control at the Drosophila midblastula transition
TLDR
This article showed that mutations in the grapes (grp) checkpoint 1 kinase homologue in Drosophila block the morphological and biochemical changes that accompany the midblastula transition, leading to a continuation of the maternal cell-cycle programme, and disrupt DNA-replication checkpoint control of cell cycle progression.Abstract:
Embryogenesis is typically initiated by a series of rapid mitotic divisions that are under maternal genetic control. The switch to zygotic control of embryogenesis at the midblastula transition is accompanied by significant increases in cell-cycle length and gene transcription, and changes in embryo morphology. Here we show that mutations in the grapes (grp) checkpoint 1 kinase homologue in Drosophila block the morphological and biochemical changes that accompany the midblastula transition, lead to a continuation of the maternal cell-cycle programme, and disrupt DNA-replication checkpoint control of cell-cycle progression. The timing of the midblastula transition is controlled by the ratio of nuclei to cytoplasm (the nucleocytoplasmic ratio), suggesting that this developmental transition is triggered by titration of a maternal factor by the increasing mass of nuclear material that accumulates during the rapid embryonic mitoses. Our observations support a model for cell-cycle control at the midblastula transition in which titration of a maternal component of the DNA-replication machinery slows DNA synthesis and induces a checkpoint-dependent delay in cell-cycle progression. This delay may allow both completion of S phase and transcription of genes that initiate the switch to zygotic control of embryogenesis.read more
Citations
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Journal ArticleDOI
Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint
Qinghua Liu,Saritha Guntuku,Xian Shu Cui,Shuhei Matsuoka,David Cortez,Katsuyuki Tamai,Guangbin Luo,Sandra Carattini-Rivera,Francisco J. DeMayo,Allan Bradley,Lawrence A. Donehower,Stephen J. Elledge +11 more
TL;DR: It is shown that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU).
Journal ArticleDOI
Conservation of the Chk1 checkpoint pathway in mammals: Linkage of DNA damage to Cdk regulation through Cdc25
Yolanda Sanchez,Calvin Wong,Calvin Wong,Richard S. Thoma,Richard S. Thoma,Ron Richman,Ron Richman,Zhiqi Wu,Zhiqi Wu,Helen Piwnica-Worms,Stephen J. Elledge,Stephen J. Elledge +11 more
TL;DR: Results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and mitotic entry.
Journal ArticleDOI
ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1.
Hui Zhao,Helen Piwnica-Worms +1 more
TL;DR: It is demonstrated that agents that block DNA replication or cause certain forms of DNA damage induce the phosphorylation of human Chk1, an evolutionarily conserved protein kinase that regulates cell cycle progression in response to checkpoint activation.
Journal ArticleDOI
Aberrant cell cycle checkpoint function and early embryonic death in Chk1 −/− mice
Hiroyuki Takai,Kaoru Tominaga,Noboru Motoyama,Yohji A. Minamishima,Hiroyasu Nagahama,Tadasuke Tsukiyama,Kyoji Ikeda,Keiko Nakayama,Makoto Nakanishi,Keiichi I. Nakayama +9 more
TL;DR: Targeted disruption of Chk1 in mice showed that ChK1(-/-) embryos exhibit gross morphologic abnormalities in nuclei as early as the blastocyst stage, which may indicate that Chk 1 is indispensable for cell proliferation and survival through maintaining the G(2) checkpoint in mammals.
Journal ArticleDOI
Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts
TL;DR: It is suggested that Xchk1 is a functionally important target of Xatr during a checkpoint response to unreplicated or UV-damaged DNA.
References
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Journal ArticleDOI
The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity
Patrick Fogarty,Shelagh D. Campbell,Robin Abu-Shumays,Brigitte de Saint Phalle,Kristina R. Yu,Geoffrey L. Uy,Michael L. Goldberg,William J. Sullivan +7 more
TL;DR: It is proposed that the primary defect in grp-derived embryos is a failure to replicate or repair DNA completely before mitotic entry during the late syncytial divisions, which suggests that wild-type grp functions in a developmentally regulated DNA replication/damage checkpoint operating during theLate syncyTial divisions.
Journal ArticleDOI
Behaviour of microtubules and actin filaments in living Drosophila embryos
TL;DR: Novel fluorescent derivatives of rabbit muscle actin and bovine tubulin are prepared and used to study the behaviour of actin filaments and microtubules in living Drosophila embryos, in which the nuclei divide at intervals of 8 to 21 min.
Journal ArticleDOI
Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio.
D K Pritchard,G Schubiger +1 more
TL;DR: It is suggested that titration of transcription factors like ttk by the nucleocytoplasmic ratio triggers zygotic transcription in Drosophila.
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Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program.
Bruce A. Edgar,Sanjeev A. Datar +1 more
TL;DR: It is proposed that Drosophila's MZT comprises a chain reaction in which proliferating nuclei deplete factors required for cell cycle progression and this depletion causes the elongation of interphases and allows zygotic transcription, which can compensate for losses or additions of nuclei by altering the timing and number of the maternal cycles.
Journal ArticleDOI
Regulation of runt transcription by Drosophila segmentation genes.
Martin Klinger,J. Peter Gergen +1 more
TL;DR: Examination of the early RNA patterns of the pair-rule genes even-skipped, hairy, and fushi tarazu indicate that they are also regulated in a similar manner and show a combination of both stripe specific and uniform regulatory effects.