Genomes and Genes
Gene Symbol: lok
Alias: 10895, 38B.4, CG10895, CHK-2, CHK2, Chk2, DmCHk2, DmChk2, Dmchk2, Dmel\CG10895, Dmnk, Dmnk-L, Dmnk-S, Dmnk/DChk2, LOKI/CHK2, MNK, chk, chk2, chk2/lok, mnk, loki, CG10895-PA, CG10895-PB, CG10895-PC, CG10895-PD, checkpoint kinase 2, drosophila maternal nuclear kinase, localized ovarian kinase, lok-PA, lok-PB, lok-PC, lok-PD, maternal nuclear kinase
Species: fruit fly
- Xu J, Du W. Drosophila chk2 plays an important role in a mitotic checkpoint in syncytial embryos. FEBS Lett. 2003;545:209-12 pubmedDrosophila chk2 (Dmchk2, also called Dmnk) plays a crucial role in the DNA damage response pathway mediating cell cycle arrest and apoptosis [Xu et al., FEBS Lett. 508 (2001) 394-398; Peters et al., Proc. Natl. Acad. Sci...
- Kurzhals R, Titen S, Xie H, Golic K. Chk2 and p53 are haploinsufficient with dependent and independent functions to eliminate cells after telomere loss. PLoS Genet. 2011;7:e1002103 pubmed publisher..Here we show that p53 and Chk2 limit the growth and differentiation of cells that lose a telomere...
- Klattenhoff C, Xi H, Li C, Lee S, Xu J, Khurana J, et al. The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters. Cell. 2009;138:1137-49 pubmed publisher..Rhino thus appears to promote transcription of dual-strand clusters, leading to production of piRNAs that drive the ping-pong amplification cycle. ..
- Wylie A, Lu W, D Brot A, Buszczak M, Abrams J. p53 activity is selectively licensed in the Drosophila stem cell compartment. elife. 2014;3:e01530 pubmed publisher..Furthermore, the findings uncover ancestral links between p53 and aberrant proliferation that are independent of DNA breaks and predate evolution of the ARF/Mdm2 axis. DOI: http://dx.doi.org/10.7554/eLife.01530.001. ..
- Bakhrat A, Pritchett T, Peretz G, McCall K, Abdu U. Drosophila Chk2 and p53 proteins induce stage-specific cell death independently during oogenesis. Apoptosis. 2010;15:1425-34 pubmed publisherIn Drosophila, the checkpoint protein-2 kinase (DmChk2) and its downstream effector protein, Dmp53, are required for DNA damage-mediated cell cycle arrest, DNA repair and apoptosis...
- Oishi I, Sugiyama S, Otani H, Yamamura H, Nishida Y, Minami Y. A novel Drosophila nuclear protein serine/threonine kinase expressed in the germline during its establishment. Mech Dev. 1998;71:49-63 pubmed..We report here the identification and developmental expression of Dmnk (Drosophila maternal nuclear kinase), a Drosophila gene encoding a putative nuclear protein serine/threonine kinase with no apparent ..
- Klattenhoff C, Bratu D, McGinnis Schultz N, Koppetsch B, Cook H, Theurkauf W. Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response. Dev Cell. 2007;12:45-55 pubmed..Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore ..
- Lee E, Trinh T, Shim H, Park S, Nguyen T, Kim M, et al. Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks. DNA Repair (Amst). 2012;11:741-52 pubmed publisher..In summary, our data suggest that Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks, and this difference is probably due to distinct phosphorylation statuses. ..
- Peng J, Karpen G. Heterochromatic genome stability requires regulators of histone H3 K9 methylation. PLoS Genet. 2009;5:e1000435 pubmed publisher..Similar effects of lower magnitude were observed in animals that lack the RNA interference pathway component Dcr2. These results suggest that the H3K9 methylation and RNAi pathways ensure heterochromatin stability. ..
- McCaffrey R, St Johnston D, González Reyes A. Drosophila mus301/spindle-C encodes a helicase with an essential role in double-strand DNA break repair and meiotic progression. Genetics. 2006;174:1273-85 pubmed..However, neither mei-W68 nor mei-41 rescue the defects in oocyte specification of mus301 mutants, suggesting that this helicase has another function in oocyte selection that is independent from its role in meiotic recombination. ..
- Sakurai H, Okado M, Ito F, Kawasaki K. Anaphase DNA bridges induced by lack of RecQ5 in Drosophila syncytial embryos. FEBS Lett. 2011;585:1923-8 pubmed publisher..of daughter nuclei that had been linked by the bridges concurrently exited from the cycle and were eliminated by Chk2-dependent centrosome inactivation...
- Khurana J, Xu J, Weng Z, Theurkauf W. Distinct functions for the Drosophila piRNA pathway in genome maintenance and telomere protection. PLoS Genet. 2010;6:e1001246 pubmed publisher..However, the aub and armi genes have an additional function in assembly of the telomere protection complex. ..
- Larocque J, Jaklevic B, Su T, Sekelsky J. Drosophila ATR in double-strand break repair. Genetics. 2007;175:1023-33 pubmed..To test this, we genetically reduced mitotic cyclin levels and also examined repair in grp (DmChk1) and lok (DmChk2) mutants...
- Mehrotra S, Maqbool S, Kolpakas A, Murnen K, Calvi B. Endocycling cells do not apoptose in response to DNA rereplication genotoxic stress. Genes Dev. 2008;22:3158-71 pubmed publisher..Similar mechanisms may operate during vertebrate development, with implications for cancer predisposition in certain tissues. ..
- Chen Y, Pane A, Schupbach T. Cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila. Curr Biol. 2007;17:637-42 pubmed..In Drosophila, a meiotic checkpoint which monitors double-stranded DNA breaks and involves Drosophila ATR and Chk2 coordinates the meiotic cell cycle with signaling events that establish the axis of the egg and embryo...
- Lu W, Chapo J, Roig I, Abrams J. Meiotic recombination provokes functional activation of the p53 regulatory network. Science. 2010;328:1278-81 pubmed publisher..Our findings establish a physiological role for p53 in meiosis and suggest that tumor-suppressive functions may have been co-opted from primordial activities linked to recombination. ..
- Rouget C, Papin C, Boureux A, Meunier A, Franco B, Robine N, et al. Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature. 2010;467:1128-32 pubmed publisher..Because the piRNAs involved in this regulation are produced from transposable elements, this identifies a direct developmental function for transposable elements in the regulation of gene expression. ..
- Titen S, Golic K. Telomere loss provokes multiple pathways to apoptosis and produces genomic instability in Drosophila melanogaster. Genetics. 2008;180:1821-32 pubmed publisher..The most prominent outcome of this event is cell death through Chk2 and Chk1 controlled p53-dependent apoptotic pathways...
- Sekelsky J, Brodsky M, Burtis K. DNA repair in Drosophila: insights from the Drosophila genome sequence. J Cell Biol. 2000;150:F31-6 pubmed
- Abdu U, Brodsky M, Schupbach T. Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk. Curr Biol. 2002;12:1645-51 pubmed..We show that a mutation in the Drosophila Chk2 homolog (DmChk2/Mnk) suppresses the defects in the translation of gurken mRNA and also the defects in oocyte nuclear morphology...
- Abdu U, Klovstad M, Butin Israeli V, Bakhrat A, Schupbach T. An essential role for Drosophila hus1 in somatic and meiotic DNA damage responses. J Cell Sci. 2007;120:1042-9 pubmed..These results demonstrate that hus1 is essential for the activation of the meiotic checkpoint and that hus1 is also required for the organization of the oocyte DNA, a function that might be independent of the meiotic checkpoint. ..
- Pane A, Wehr K, Schupbach T. zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev Cell. 2007;12:851-62 pubmed..We show that these defects are due to the inability of zuc and squ mutants to produce repeat-associated small interfering RNAs. ..
- Blumenstiel J, Fu R, Theurkauf W, Hawley R. Components of the RNAi machinery that mediate long-distance chromosomal associations are dispensable for meiotic and early somatic homolog pairing in Drosophila melanogaster. Genetics. 2008;180:1355-65 pubmed publisher..Thus, there appears to be at least two mechanisms that bring homologous sequences together within the nucleus: those that act between dispersed homologous sequences and those that act to align and pair homologous chromosomes. ..
- Wichmann A, Jaklevic B, Su T. Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell death in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2006;103:9952-7 pubmed..In mutants of Drosophila Chk2 or p53 homologs, apoptosis is severely diminished in these assays, leading to the widely held belief that IR-..
- McNamee L, Brodsky M. p53-independent apoptosis limits DNA damage-induced aneuploidy. Genetics. 2009;182:423-35 pubmed publisher..We propose that reduced copy number of haploinsufficient genes following chromosome damage activates apoptosis and helps maintain genomic integrity. ..
- Peters M, DeLuca C, Hirao A, Stambolic V, Potter J, Zhou L, et al. Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila. Proc Natl Acad Sci U S A. 2002;99:11305-10 pubmed..This phenotype was markedly enhanced by coexpression with D. melanogaster Chk2 (DmChk2) and was almost fully rescued by coexpression with a dominant-negative (DN), kinase-dead form of DmChk2...
- Yamasaki S, Yagishita N, Sasaki T, Nakazawa M, Kato Y, Yamadera T, et al. Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'. EMBO J. 2007;26:113-22 pubmed..Our results provide novel insights into p53 signaling mediated by Synoviolin. ..
- Higa L, Mihaylov I, Banks D, Zheng J, Zhang H. Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nat Cell Biol. 2003;5:1008-15 pubmed..We show that radiation-mediated CDT1 proteolysis is independent of ATM and CHK2 and can occur in G1-phase cells...
- Iampietro C, Bergalet J, Wang X, Cody N, Chin A, Lefebvre F, et al. Developmentally regulated elimination of damaged nuclei involves a Chk2-dependent mechanism of mRNA nuclear retention. Dev Cell. 2014;29:468-81 pubmed publisher..We show that this involves a Chk2-dependent mechanism of mRNA nuclear retention that is induced by DNA damage and prevents the translation of ..
- Loh B, Cullen C, Vogt N, Ohkura H. The conserved kinase SRPK regulates karyosome formation and spindle microtubule assembly in Drosophila oocytes. J Cell Sci. 2012;125:4457-62 pubmed publisher..Subsequently, bi-orientation and segregation of meiotic chromosomes are also defective. Therefore, this study demonstrates new roles of this conserved kinase in two independent meiotic steps specific to oocytes. ..
- Mika S, Rost B. Protein-protein interactions more conserved within species than across species. PLoS Comput Biol. 2006;2:e79 pubmed..More comprehensive images of protein-protein networks will require the combination of many high-throughput methods, including in silico inferences and predictions. http://www.rostlab.org/results/2006/ppi_homology/ ..
- Benoit B, He C, Zhang F, Votruba S, Tadros W, Westwood J, et al. An essential role for the RNA-binding protein Smaug during the Drosophila maternal-to-zygotic transition. Development. 2009;136:923-32 pubmed publisher..Smaug accumulation thus coordinates progression through the MZT. ..
- Atikukke G, Albosta P, Zhang H, Finley R. A role for Drosophila Cyclin J in oogenesis revealed by genetic interactions with the piRNA pathway. Mech Dev. 2014;133:64-76 pubmed publisher..these compound egg chambers could be suppressed with CycJ transgenes but not with mutations in the checkpoint gene mnk, which suppress oogenesis defects in armi mutants...
- Klovstad M, Abdu U, Schupbach T. Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint. PLoS Genet. 2008;4:e31 pubmed publisher..In addition, Brca2 co-immunoprecipitates with the checkpoint protein Rad9, suggesting a direct role for Brca2 in the transduction of the meiotic recombination checkpoint signal. ..
- Maezawa T, Arita K, Shigenobu S, Kobayashi S. Expression of the apoptosis inducer gene head involution defective in primordial germ cells of the Drosophila embryo requires eiger, p53, and loki function. Dev Growth Differ. 2009;51:453-61 pubmed publisher..In addition, we demonstrate that p53 and loki (lok), a damage-activated kinase known to be required for p53 phosphorylation, are both required for hid expression ..
- Nagel A, Fischer P, Szawinski J, La Rosa M, Preiss A. Cyclin G is involved in meiotic recombination repair in Drosophila melanogaster. J Cell Sci. 2012;125:5555-63 pubmed publisher..the downregulation of Mei-W68 (an endonuclease that induces meiotic DSBs), Mei-41, or Drosophila melanogaster Chk2 (a downstream kinase that initiates the meiotic checkpoint) rescues the cycG mutant eggshell phenotype...
- Shaposhnikov M, Proshkina E, Shilova L, Zhavoronkov A, Moskalev A. Lifespan and Stress Resistance in Drosophila with Overexpressed DNA Repair Genes. Sci Rep. 2015;5:15299 pubmed publisher..Overexpressed genes included those involved in recognition of DNA damage (homologs of HUS1, CHK2), nucleotide and base excision repair (homologs of XPF, XPC and AP-endonuclease-1), and repair of double-stranded ..
- Lee S, Bang S, Lee J, Cho K. Evaluation of traditional medicines for neurodegenerative diseases using Drosophila models. Evid Based Complement Alternat Med. 2014;2014:967462 pubmed publisher..Here, we introduce the Drosophila model for neurodegenerative diseases and some examples demonstrating the successful application of Drosophila models in the evaluation of traditional medicines. ..
- Poulton J, Mu F, Roberts D, Peifer M. APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation. Development. 2013;140:4226-36 pubmed publisher..Our in vivo data demonstrate that APC2 protects genome stability by modulating mitotic fidelity through regulation of the cytoskeleton. ..
- Pushpavalli S, Sarkar A, Ramaiah M, Chowdhury D, Bhadra U, Pal Bhadra M. Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis. BMC Mol Biol. 2013;14:1 pubmed publisher..MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue...
- Iijima K, Gatt A, Iijima Ando K. Tau Ser262 phosphorylation is critical for Abeta42-induced tau toxicity in a transgenic Drosophila model of Alzheimer's disease. Hum Mol Genet. 2010;19:2947-57 pubmed publisher..We have recently reported that the DNA damage-activated Checkpoint kinase 2 (Chk2) phosphorylates tau at Ser262 and enhances tau toxicity in a transgenic Drosophila model...
- Milan M, Clemente Ruiz M, Dekanty A, Muzzopappa M. Aneuploidy and tumorigenesis in Drosophila. Semin Cell Dev Biol. 2014;28:110-5 pubmed publisher..Here we discuss the role of aneuploidy in tumorigenesis in light of the contribution of Drosophila epithelial cancer models and propose a stress-induced tumor-promoting role of aneuploidy. ..
- Sato K, Nishida K, Shibuya A, Siomi M, Siomi H. Maelstrom coordinates microtubule organization during Drosophila oogenesis through interaction with components of the MTOC. Genes Dev. 2011;25:2361-73 pubmed publisher..This results from the activation of the DNA damage checkpoint factor Checkpoint kinase 2 (Chk2) due to transposon derepression...
- Stumpff J, Kellogg D, Krohne K, Su T. Drosophila Wee1 interacts with members of the gammaTURC and is required for proper mitotic-spindle morphogenesis and positioning. Curr Biol. 2005;15:1525-34 pubmed..Instead, dWee1 is also required for phosphorylation of gamma-tubulin, centrosome positioning, and mitotic-spindle integrity. We propose a model to account for these requirements. ..
- Titen S, Lin H, Bhandari J, Golic K. Chk2 and p53 regulate the transmission of healed chromosomes in the Drosophila male germline. PLoS Genet. 2014;10:e1004130 pubmed publisher..We find that Chk2 (encoded by lok) and P53, major mediators of the DNA damage response, have strong and opposite influences on the ..
- Takada S, Kwak S, Koppetsch B, Theurkauf W. grp (chk1) replication-checkpoint mutations and DNA damage trigger a Chk2-dependent block at the Drosophila midblastula transition. Development. 2007;134:1737-44 pubmed..The mnk (also known as loki) gene encodes Checkpoint kinase 2 (Chk2), which functions in DNA-damage signal transduction...
- GÃ¼nesdogan U, JÃ¤ckle H, Herzig A. Histone supply regulates S phase timing and cell cycle progression. elife. 2014;3:e02443 pubmed publisher..Our results suggest a novel cell cycle surveillance mechanism that monitors nucleosome assembly without involving the DNA repair pathways and exerts its effect via suppression of CDC25 phosphatase String expression. ..
- Baehrecke E. Growth control: p53, the guardian angel of compensatory proliferation. Curr Biol. 2006;16:R840-2 pubmed..Recent work has revealed a new role for Drosophila p53 in the compensatory proliferation of cells that are needed to repair damaged tissues, a role that requires the non-apoptotic function of the caspase protease Dronc. ..
- Yi X, Lemstra W, Vos M, Shang Y, Kampinga H, Su T, et al. A long-term flow cytometry assay to analyze the role of specific genes of Drosophila melanogaster S2 cells in surviving genotoxic stress. Cytometry A. 2008;73:637-42 pubmed publisher..we validate this assay and we used this novel method to investigate the role of checkpoint genes grapes/Dchk1 and DmChk2 in cell survival responses...
- Wallace H, Merkle J, Yu M, Berg T, Lee E, Bosco G, et al. TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase ?. Development. 2014;141:1332-41 pubmed publisher..barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint...
- Rickmyre J, Dasgupta S, Ooi D, Keel J, Lee E, Kirschner M, et al. The Drosophila homolog of MCPH1, a human microcephaly gene, is required for genomic stability in the early embryo. J Cell Sci. 2007;120:3565-77 pubmed..Mutation of Chk2 suppresses these defects, indicating that they occur secondary to a previously described Chk2-mediated response to ..
- Stumpff J, Duncan T, Homola E, Campbell S, Su T. Drosophila Wee1 kinase regulates Cdk1 and mitotic entry during embryogenesis. Curr Biol. 2004;14:2143-8 pubmed..dwee1 leads to premature entry into mitosis, mitotic spindle defects, chromosome condensation problems, and a Chk2-dependent block of subsequent development, and then embryonic lethality...
- Di Talia S, She R, Blythe S, Lu X, Zhang Q, Wieschaus E. Posttranslational control of Cdc25 degradation terminates Drosophila's early cell-cycle program. Curr Biol. 2013;23:127-32 pubmed publisher..We demonstrate that posttranslational control of Twine degradation ensures that the proper number of mitoses precede the MBT. ..
- Raff J. Cell division: Genome maintenance. Nature. 2003;423:493, 495 pubmed
- Tran M, Tsarouhas V, Kegel A. Early development of Drosophila embryos requires Smc5/6 function during oogenesis. Biol Open. 2016;5:928-41 pubmed publisher..Thus, our findings contribute to the understanding of Smc proteins in higher eukaryotic development by highlighting a maternal function in chromosome maintenance and a link between oogenesis and early embryogenesis. ..
- Cavey M, Hijal S, Zhang X, Suter B. Drosophila valois encodes a divergent WD protein that is required for Vasa localization and Oskar protein accumulation. Development. 2005;132:459-68 pubmed..Based on the structure of Vls, the function of similar proteins in different systems and our phenotypic analysis, it seems likely that vls may promote posterior patterning by facilitating interactions between different molecules. ..
- Becalska A, Kim Y, Belletier N, Lerit D, Sinsimer K, Gavis E. Aubergine is a component of a nanos mRNA localization complex. Dev Biol. 2011;349:46-52 pubmed publisher..Aub interacts with nos mRNA in vivo and co-purifies with Rump in an RNA-dependent manner. Our results support a role for Aub, independent of its function in RNA silencing, as a component of a nos mRNA localization complex...
- Yamaki T, Yasuda G, Wakimoto B. The Deadbeat Paternal Effect of Uncapped Sperm Telomeres on Cell Cycle Progression and Chromosome Behavior in Drosophila melanogaster. Genetics. 2016;203:799-816 pubmed publisher..Progression past cycle 3 can also occur if embryos have reduced levels of the maternally provided checkpoint kinase Chk2. The findings provide insights into how telomere integrity affects the regulation of the earliest embryonic cell ..
- Oikemus S, Queiroz Machado J, Lai K, McGinnis N, Sunkel C, Brodsky M. Epigenetic telomere protection by Drosophila DNA damage response pathways. PLoS Genet. 2006;2:e71 pubmed..Given the conserved roles of DNA damage response proteins in telomere function, related mechanisms may act at the telomeres of other organisms. ..
- Shim H, Lee E, Nguyen L, Shim J, Song Y. High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis. PLoS ONE. 2014;9:e89009 pubmed publisher..high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner...
- Farrell J, O Farrell P. Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling. Curr Biol. 2013;23:118-26 pubmed publisher..Moreover, we show that this destruction is triggered by the nucleocytoplasmic ratio-dependent onset of zygotic transcription of tribbles and other unknown genes. ..
- Hamada Kawaguchi N, Nore B, Kuwada Y, Smith C, Yamamoto D. Btk29A promotes Wnt4 signaling in the niche to terminate germ cell proliferation in Drosophila. Science. 2014;343:294-7 pubmed publisher..This signaling mechanism likely represents a versatile developmental switch. ..
- Gomes A, Nolasco S, Soares H. Non-coding RNAs: multi-tasking molecules in the cell. Int J Mol Sci. 2013;14:16010-39 pubmed publisher..We also highlighted the implications of biogenesis and gene expression deregulation of sncRNAs and lncRNAs in human diseases like cancer. ..
- Alexander J, Barrasa M, Orr Weaver T. Replication fork progression during re-replication requires the DNA damage checkpoint and double-strand break repair. Curr Biol. 2015;25:1654-60 pubmed publisher..NHEJ appears to continually repair forks during re-replication to maintain elongation. ..
- Park S, Song Y. Genetic screen for genes involved in Chk2 signaling in Drosophila. Mol Cells. 2008;26:350-5 pubmedb>Chk2 is a well characterized protein kinase with key roles in the DNA damage response...
- Papaconstantinou M, Pepper A, Wu Y, Kasimer D, Westwood T, Campos A, et al. Menin links the stress response to genome stability in Drosophila melanogaster. PLoS ONE. 2010;5:e14049 pubmed publisher..Therefore, menin links the stress response to the control of genome stability in Drosophila melanogaster. ..
- Ma X, Han Y, Song X, Do T, Yang Z, Ni J, et al. DNA damage-induced Lok/CHK2 activation compromises germline stem cell self-renewal and lineage differentiation. Development. 2016;143:4312-4323 pubmed..this study, we show that DNA damage retards germline stem cell (GSC) self-renewal and progeny differentiation in a Lok kinase-dependent manner in the Drosophila ovary...