{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:31:27Z","timestamp":1789201887951,"version":"build-2803163510"},"reference-count":36,"publisher":"The Company of Biologists","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,8,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1242\/jcs.02454","type":"journal-article","created":{"date-parts":[[2005,8,3]],"date-time":"2005-08-03T18:23:54Z","timestamp":1123093434000},"page":"3305-3315","source":"Crossref","is-referenced-by-count":17,"title":["Regulation of mitosis in response to damaged or incompletely replicated DNA require different levels of Grapes (<i>Drosophila<\/i>Chk1)"],"prefix":"10.1242","volume":"118","author":[{"given":"Amanda","family":"Purdy","sequence":"first","affiliation":[{"name":"MCD Biology, University of Colorado, Boulder, CO 80309-0347, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyle","family":"Uyetake","sequence":"additional","affiliation":[{"name":"MCD Biology, University of Colorado, Boulder, CO 80309-0347, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa Garner","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"MCD Biology, University of Colorado, Boulder, CO 80309-0347, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tin Tin","family":"Su","sequence":"additional","affiliation":[{"name":"MCD Biology, University of Colorado, Boulder, CO 80309-0347, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042519035104400_REF1","doi-asserted-by":"crossref","unstructured":"Boddy, M. N., Furnari, B., Mondesert, O. and Russell, P. (1998). Replication checkpoint enforced by kinases Cds1 and Chk1. Science280, 909-912.","DOI":"10.1126\/science.280.5365.909"},{"key":"2021042519035104400_REF2","doi-asserted-by":"crossref","unstructured":"Brodsky, M. H., Sekelsky, J. J., Tsang, G., Hawley, R. S. and Rubin, G. M. (2000). mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development. Genes Dev.14, 666-678.","DOI":"10.1101\/gad.14.6.666"},{"key":"2021042519035104400_REF3","doi-asserted-by":"crossref","unstructured":"Brodsky, M. H., Weinert, B. T., Tsang, G., Rong, Y. S., McGinnis, N. M., Golic, K. G., Rio, D. C. and Rubin, G. M. (2004). Drosophila melanogaster MNK\/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage. Mol. Cell. Biol.3, 1219-1231.","DOI":"10.1128\/MCB.24.3.1219-1231.2004"},{"key":"2021042519035104400_REF4","doi-asserted-by":"crossref","unstructured":"Brondello, J. M., Boddy, M. N., Furnari, B. and Russell, P. (1999). Basis for the checkpoint signal specificity that regulates Chk1 and Cds1 protein kinases. Mol. Cell. Biol.19, 4262-4269.","DOI":"10.1128\/MCB.19.6.4262"},{"key":"2021042519035104400_REF5","doi-asserted-by":"crossref","unstructured":"Clarkson, M. and Saint, R. (1999). A His2AvDGFP fusion gene complements a lethal His2AvD mutant allele and provides an in vivo marker for Drosophila chromosome behavior. DNA Cell Biol.18, 457-462.","DOI":"10.1089\/104454999315178"},{"key":"2021042519035104400_REF6","doi-asserted-by":"crossref","unstructured":"D'Urso, G., Grallert, B. and Nurse, P. (1995). DNA polymerase alpha, a component of the replication initiation complex, is essential for the checkpoint coupling S phase to mitosis in fission yeast. J. Cell Sci.108, 3109-3118.","DOI":"10.1242\/jcs.108.9.3109"},{"key":"2021042519035104400_REF7","unstructured":"Foe, V. E., Odell, G. M. and Edgar, B. A. (1993). Mitosis and morphogenesis in the Drosophila embryo. In The Development of Drosophila melanogaster. Cold Spring Harbor: Cold Spring Harbor Press."},{"key":"2021042519035104400_REF8","doi-asserted-by":"crossref","unstructured":"Fogarty, P., Kalpin, R. F. and Sullivan, W. (1994). The Drosophila maternal-effect mutation grapes causes a metaphase arrest at nuclear cycle 13. Development120, 2131-2142.","DOI":"10.1242\/dev.120.8.2131"},{"key":"2021042519035104400_REF9","doi-asserted-by":"crossref","unstructured":"Fogarty, P., Campbell, S. D., Abu-Shumays, R., Phalle, B. S., Yu, K. R., Uy, G. L., Goldberg, M. L. and Sullivan, W. (1997). The Drosophila grapes gene is related to checkpoint gene chk1\/rad27 and is required for late syncytial division fidelity. Curr. Biol.7, 418-426.","DOI":"10.1016\/S0960-9822(06)00189-8"},{"key":"2021042519035104400_REF10","doi-asserted-by":"crossref","unstructured":"Garber, P. M. and Rine, J. (2002). Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell cycle response to altered chromosomes in Saccharomyces cerevisiae.Genetics161, 521-534.","DOI":"10.1093\/genetics\/161.2.521"},{"key":"2021042519035104400_REF11","doi-asserted-by":"crossref","unstructured":"Garner, M., van Kreeveld, S. and Su, T. T. (2001). mei-41 and bub1 block mitosis at two distinct steps in response to incomplete DNA replication in Drosophila embryos. Curr. Biol.11, 1595-1599.","DOI":"10.1016\/S0960-9822(01)00483-3"},{"key":"2021042519035104400_REF12","doi-asserted-by":"crossref","unstructured":"Guo, Z., Kumagai, A., Wang, S. X. and Dunphy, W. G. (2000). 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. Genes Dev.14, 2745-2756.","DOI":"10.1101\/gad.842500"},{"key":"2021042519035104400_REF13","doi-asserted-by":"crossref","unstructured":"Jaklevic, B. R. and Su, T. T. (2004). Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae. Curr. Biol.14, 23-32.","DOI":"10.1016\/j.cub.2003.12.032"},{"key":"2021042519035104400_REF14","doi-asserted-by":"crossref","unstructured":"Krishnan, V., Nirantar, S., Crasta, K., Cheng, A. Y. and Surana, U. (2004). DNA replication checkpoint prevents precocious chromosome segregation by regulating spindle behavior. Mol. Cell16, 687-700.","DOI":"10.1016\/j.molcel.2004.11.001"},{"key":"2021042519035104400_REF15","doi-asserted-by":"crossref","unstructured":"Laurencon, A., Purdy, A., Sekelsky, J., Hawley, R. S. and Su, T. T. (2003). Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM\/ATR. Genetics164, 589-601.","DOI":"10.1093\/genetics\/164.2.589"},{"key":"2021042519035104400_REF16","doi-asserted-by":"crossref","unstructured":"Liu, Q., Guntuku, S., Cui, X. S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A. et al. (2000). Chk1 is an essential kinase that is regulated by Atr and required for the G(2)\/M DNA damage checkpoint. Genes Dev.14, 1448-1459.","DOI":"10.1101\/gad.14.12.1448"},{"key":"2021042519035104400_REF17","doi-asserted-by":"crossref","unstructured":"Melo, J. and Toczyski, D. (2002). A unified view of the DNA-damage checkpoint. Curr. Opin. Cell Biol.14, 237-245.","DOI":"10.1016\/S0955-0674(02)00312-5"},{"key":"2021042519035104400_REF18","doi-asserted-by":"crossref","unstructured":"Mikhailov, A., Cole, R. W. and Rieder, C. L. (2002). DNA damage during mitosis in human cells delays the metaphase\/anaphase transition via the spindle-assembly checkpoint. Curr. Biol.12, 1797-1806.","DOI":"10.1016\/S0960-9822(02)01226-5"},{"key":"2021042519035104400_REF19","doi-asserted-by":"crossref","unstructured":"Motoyama, N. and Naka, K. (2004). DNA damage tumor suppressor genes and genomic instability. Curr. Opin. Genet. Dev.14, 11-16.","DOI":"10.1016\/j.gde.2003.12.003"},{"key":"2021042519035104400_REF20","doi-asserted-by":"crossref","unstructured":"Piatti, S., Lengauer, C. and Nasmyth, K. (1995). Cdc6 is an unstable protein whose de novo synthesis in G1 is important for the onset of S phase and for preventing a `reductional' anaphase in the budding yeast Saccharomyces cerevisiae.EMBO J.14, 3788-3799.","DOI":"10.1002\/j.1460-2075.1995.tb00048.x"},{"key":"2021042519035104400_REF21","doi-asserted-by":"crossref","unstructured":"Rhind, N. and Russell, P. (2000). Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. J. Cell Sci.113, 3889-3896.","DOI":"10.1242\/jcs.113.22.3889"},{"key":"2021042519035104400_REF22","doi-asserted-by":"crossref","unstructured":"Rieder, C. L. and Cole, R. W. (1998). Entry into mitosis in vertebrate somatic cells is guarded by a chromosome damage checkpoint that reverses the cell cycle when triggered during early but not late prophase. J. Cell Biol.142, 1013-1022.","DOI":"10.1083\/jcb.142.4.1013"},{"key":"2021042519035104400_REF23","doi-asserted-by":"crossref","unstructured":"Royou, A., Macias, H. and Sullivan, W. (2005). The Drosophila Grp\/Chk1 DNA damage checkpoint controls entry into anaphase. Curr. Biol.15, 34-39.","DOI":"10.1016\/j.cub.2005.02.026"},{"key":"2021042519035104400_REF24","doi-asserted-by":"crossref","unstructured":"Sanchez, Y., Bachant, J., Wang, H., Hu, F., Liu, D., Tetzlaff, M. and Elledge, S. J. (1999). Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science286, 1166-1171.","DOI":"10.1126\/science.286.5442.1166"},{"key":"2021042519035104400_REF25","doi-asserted-by":"crossref","unstructured":"Sibon, O. C., Stevenson, V. A. and Theurkauf, W. E. (1997). 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Drosophila checkpoint kinase 2 couples centrosome function and spindle assembly to genomic integrity. Cell113, 87-99.","DOI":"10.1016\/S0092-8674(03)00202-2"},{"key":"2021042519035104400_REF33","doi-asserted-by":"crossref","unstructured":"Takai, H., Tominaga, K., Motoyama, N., Minamishima, Y. A., Nagahama, H., Tsukiyama, T., Ikeda, K., Nakayama, K. and Nakanishi, M. (2000). Aberrant cell cycle checkpoint function and early embryonic death in Chk1(\u2013\/\u2013) mice. Genes Dev.14, 1439-1447.","DOI":"10.1101\/gad.14.12.1439"},{"key":"2021042519035104400_REF34","doi-asserted-by":"crossref","unstructured":"Walworth, N. C. and Bernards, R. (1996). rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. Science271, 353-356.","DOI":"10.1126\/science.271.5247.353"},{"key":"2021042519035104400_REF35","doi-asserted-by":"crossref","unstructured":"Whittaker, A. J., Royzman, I. and Orr-Weaver, T. L. (2000). Drosophila double parked: a conserved, essential replication protein that colocalizes with the origin recognition complex and links DNA replication with mitosis and the down-regulation of S phase transcripts. Genes Dev.14, 1765-1776.","DOI":"10.1101\/gad.14.14.1765"},{"key":"2021042519035104400_REF36","doi-asserted-by":"crossref","unstructured":"Zhou, B. B. and Elledge, S. J. (2000). The DNA damage response: putting checkpoints in perspective. Nature408, 433-439.","DOI":"10.1038\/35044005"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/118\/15\/3305\/1525092\/3305.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/118\/15\/3305\/1525092\/3305.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:14:06Z","timestamp":1683159246000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/118\/15\/3305\/28460\/Regulation-of-mitosis-in-response-to-damaged-or"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,1]]},"references-count":36,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2005,8,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.02454","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2005,8,1]]}}}