Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Cell Sci
2005 May 01;118Pt 9:1833-42. doi: 10.1242/jcs.02309.
Show Gene links
Show Anatomy links
Grp/DChk1 is required for G2-M checkpoint activation in Drosophila S2 cells, whereas Dmnk/DChk2 is dispensable.
de Vries HI
,
Uyetake L
,
Lemstra W
,
Brunsting JF
,
Su TT
,
Kampinga HH
,
Sibon OC
.
???displayArticle.abstract???
Cell-cycle checkpoints are signal-transduction pathways required to maintain genomic stability in dividing cells. Previously, it was reported that two kinases essential for checkpoint signalling, Chk1 and Chk2 are structurally conserved. In contrast to yeast, Xenopus and mammals, the Chk1- and Chk2-dependent pathways in Drosophila are not understood in detail. Here, we report the function of these checkpoint kinases, referred to as Grp/DChk1 and Dmnk/DChk2 in Drosophila Schneider's cells, and identify an upstream regulator as well as downstream targets of Grp/DChk1. First, we demonstrate that S2 cells are a suitable model for G(2)/M checkpoint studies. S2 cells display Grp/DChk1-dependent and Dmnk/DChk2-independent cell-cycle-checkpoint activation in response to hydroxyurea and ionizing radiation. S2 cells depleted for Grp/DChk1 using RNA interference enter mitosis in the presence of impaired DNA integrity, resulting in prolonged mitosis and mitotic catastrophe. Grp/DChk1 is phosphorylated in a Mei-41/DATR-dependent manner in response to hydroxyurea and ionizing radiation, indicating that Mei-41/ATR is an upstream component in the Grp/DChk1 DNA replication and DNA-damage-response pathways. The level of Cdc25(Stg) and phosphorylation status of Cdc2 are modulated in a Grp/DChk1-dependent manner in response to hydroxyurea and irradiation, indicating that these cell-cycle regulators are downstream targets of the Grp/DChk1-dependent DNA replication and DNA-damage responses. By contrast, depletion of Dmnk/DChk2 by RNA interference had little effect on checkpoint responses to hydroxyurea and irradiation. We conclude that Grp/DChk1, and not Dmnk/DChk2, is the main effector kinase involved in G(2)/M checkpoint control in Drosophila cells.
Allen,
The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast.
1994, Pubmed
Allen,
The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast.
1994,
Pubmed
Boddy,
Replication checkpoint enforced by kinases Cds1 and Chk1.
1998,
Pubmed
Boddy,
DNA replication checkpoint control.
1999,
Pubmed
Brauchle,
Differential activation of the DNA replication checkpoint contributes to asynchrony of cell division in C. elegans embryos.
2003,
Pubmed
Brodsky,
Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage.
2004,
Pubmed
Brodsky,
mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development.
2000,
Pubmed
Brown,
A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage.
1999,
Pubmed
Chaturvedi,
Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.
1999,
Pubmed
Clemens,
Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways.
2000,
Pubmed
Donzelli,
Dual mode of degradation of Cdc25 A phosphatase.
2002,
Pubmed
Echard,
Terminal cytokinesis events uncovered after an RNAi screen.
2004,
Pubmed
Edgar,
Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis.
1994,
Pubmed
Flaggs,
Atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes.
1997,
Pubmed
Fogarty,
The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity.
1997,
Pubmed
Furnari,
Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase.
1997,
Pubmed
Goshima,
The roles of microtubule-based motor proteins in mitosis: comprehensive RNAi analysis in the Drosophila S2 cell line.
2003,
Pubmed
Guo,
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.
2000,
Pubmed
,
Xenbase
Hartwell,
Checkpoints: controls that ensure the order of cell cycle events.
1989,
Pubmed
Heffernan,
An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage.
2002,
Pubmed
Hekmat-Nejad,
Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint.
,
Pubmed
,
Xenbase
Hirao,
DNA damage-induced activation of p53 by the checkpoint kinase Chk2.
2000,
Pubmed
Hut,
Centrosomes split in the presence of impaired DNA integrity during mitosis.
2003,
Pubmed
Jaklevic,
Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae.
2004,
Pubmed
Kellogg,
CP60: a microtubule-associated protein that is localized to the centrosome in a cell cycle-specific manner.
1995,
Pubmed
,
Xenbase
Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase
Laurençon,
Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM/ATR.
2003,
Pubmed
Lindsay,
S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe.
1998,
Pubmed
Liu,
Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint.
2000,
Pubmed
Masrouha,
The Drosophila chk2 gene loki is essential for embryonic DNA double-strand-break checkpoints induced in S phase or G2.
2003,
Pubmed
Matsuoka,
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.
1998,
Pubmed
Melo,
A unified view of the DNA-damage checkpoint.
2002,
Pubmed
,
Xenbase
Murakami,
A kinase from fission yeast responsible for blocking mitosis in S phase.
1995,
Pubmed
Nakajo,
Involvement of Chk1 kinase in prophase I arrest of Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Oishi,
A novel Drosophila nuclear protein serine/threonine kinase expressed in the germline during its establishment.
1998,
Pubmed
Peng,
Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.
1997,
Pubmed
Peters,
Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila.
2002,
Pubmed
Rhind,
Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways.
2000,
Pubmed
Sanchez,
Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways.
1996,
Pubmed
Sanchez,
Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.
1997,
Pubmed
Sanchez,
Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms.
1999,
Pubmed
Shimuta,
Chk1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition.
2002,
Pubmed
,
Xenbase
Sibon,
DNA-replication checkpoint control at the Drosophila midblastula transition.
1997,
Pubmed
Sibon,
The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition.
1999,
Pubmed
Smits,
Checking out the G(2)/M transition.
2001,
Pubmed
Sun,
Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways.
1996,
Pubmed
Takai,
Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice.
2000,
Pubmed
Tominaga,
Role of human Cds1 (Chk2) kinase in DNA damage checkpoint and its regulation by p53.
1999,
Pubmed
Walworth,
Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2.
1993,
Pubmed
Walworth,
rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint.
1996,
Pubmed
Xu,
Drosophila Chk2 is required for DNA damage-mediated cell cycle arrest and apoptosis.
2001,
Pubmed
Zeng,
Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1.
1998,
Pubmed
Zhao,
ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1.
2001,
Pubmed
Zhou,
The DNA damage response: putting checkpoints in perspective.
2000,
Pubmed
al-Khodairy,
Identification and characterization of new elements involved in checkpoint and feedback controls in fission yeast.
1994,
Pubmed
