Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks

Lee, Eun-Mi; Trinh, Tram T. B.; Shim, Hongjin; Park, Su Kyoung; Nguyen, Trang; Kim, Min‐Joo; Song, Young-Han

doi:10.1016/j.dnarep.2012.06.007

Cited by 18 publications

(23 citation statements)

References 39 publications

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“…We also observed an increase in viability of double‐mutant flies (Table ). We confirmed these results by using three additional hypomorphic alleles of claspin, claspin 279 , claspin aq4 , and claspin aq5 , which could all partially rescue Rpp30 mutant phenotypes (Table ) (Lee et al , ). We further noticed an inverse correlation between the strength of the allele and the degree of rescue, with the weakest alleles rescuing the best ( claspin aq4 < claspin 279 < claspin aq5 ).…”

Section: Resultssupporting

confidence: 66%

“…Depending on the species, replication stress activates the ATR/Chk1/Claspin pathway, the ATM/Chk2 pathway, or both. In Drosophila , Claspin appears most specific to replication stress (Lee et al , ), as Chk1 and Chk2 respond to a wider range of DNA damages (Reinhardt & Yaffe, ). Furthermore, Claspin is part of the replication fork machinery and is required for efficient replication (Lou et al , ; Scorah & McGowan, ).…”

Section: Resultsmentioning

confidence: 99%

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tRNA processing defects induce replication stress and Chk2‐dependent disruption of piRNA transcription

et al. 2015

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RNase P is a conserved endonuclease that processes the 5 0 trailer of tRNA precursors. We have isolated mutations in Rpp30, a subunit of RNase P, and find that these induce complete sterility in Drosophila females. Here, we show that sterility is not due to a shortage of mature tRNAs, but that atrophied ovaries result from the activation of several DNA damage checkpoint proteins, including p53, Claspin, and Chk2. Indeed, we find that tRNA processing defects lead to increased replication stress and de-repression of transposable elements in mutant ovaries. We also report that transcription of major piRNA sources collapse in mutant germ cells and that this correlates with a decrease in heterochromatic H3K9me3 marks on the corresponding piRNA-producing loci. Our data thus link tRNA processing, DNA replication, and genome defense by small RNAs. This unexpected connection reveals constraints that could shape genome organization during evolution.

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

tRNA processing defects induce replication stress and Chk2‐dependent disruption of piRNA transcription

et al. 2015

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“…The hatch rate was calculated by the number of larvae generated from the eggs in each collection. The bristle defects were examined as previously described [9].…”

Section: Methodsmentioning

confidence: 99%

High-Dose Irradiation Induces Cell Cycle Arrest, Apoptosis, and Developmental Defects during Drosophila Oogenesis

et al. 2014

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Ionizing radiation (IR) treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs) generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis.

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“…Work in Xenopus showed that Chk1, a checkpoint kinases acting in a pathway that suppresses cyclin/Cdk1, is progressively activated in early cycles in response to increasing DNA (14). In line with this, the fly homolog of this kinase, encoded by grapes, together with the other genes in this checkpoint pathway, is responsible for a progressively increasing delay in entry into mitosis in Drosophila embryos (40, 41,49,50). A recent report suggested that activation of the checkpoint in Drosophila is coupled to N/C and that the activating signal is substantially dependent on complexes formed on promoters early in cycle 13 (22).…”

Section: When Is Mbt?mentioning

confidence: 91%

Interphase-arrestedDrosophilaembryos initiate Mid-Blastula Transition at a low nuclear-cytoplasmic ratio

Strong

Yuan

O’Farrell

2017

Preprint

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Impact statement:By showing that cell-cycle arrest allows early Drosophila embryos to progress to later stages, this work eliminates numerous models for embryonic timing and shows the dominating influence of cell-cycle slowing. AbstractExternally deposited eggs begin development with an immense cytoplasm and a single overwhelmed nucleus. Rapid mitotic cycles restore normality as the ratio of nuclei to cytoplasm (N/C) increases. At the 14th cell cycle in Drosophila embryos, the cell cycle slows, transcription increases, and morphogenesis begins at the Mid-Blastula Transition (MBT). To explore the role of N/C in MBT timing, we blocked N/C-increase by downregulating cyclin/Cdk1 to arrest early cell cycles. Embryos arrested in cell cycle 12 cellularized, initiated gastrulation movements and activated transcription of genes previously described as N/C dependent. Thus, occurrence of these events is not directly coupled to N/Cincrease.However, N/C might act indirectly. Increasing N/C promotes cyclin/Cdk1 downregulation which otherwise inhibits many MBT events. By experimentally inducing downregulation of cyclin/Cdk1, we bypassed this input of N/C-increase. We describe a regulatory cascade wherein the increasing N/C downregulates cyclin/Cdk1 to promote increasing transcription and the MBT.

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Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks

Cited by 18 publications

References 39 publications

tRNA processing defects induce replication stress and Chk2‐dependent disruption of piRNA transcription

tRNA processing defects induce replication stress and Chk2‐dependent disruption of piRNA transcription

High-Dose Irradiation Induces Cell Cycle Arrest, Apoptosis, and Developmental Defects during Drosophila Oogenesis

Interphase-arrestedDrosophilaembryos initiate Mid-Blastula Transition at a low nuclear-cytoplasmic ratio

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