Disease relevance of lok

• Chk2 is a major target of ataxia telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) [1].
• Germline mutations in Chk2 have been identified in a subset of patients with Li-Fraumeni syndrome, suggesting that Chk2 is a tumor suppressor gene [1].

High impact information on lok

• We also show that Chk2- and p53-independent apoptosis is IR dose-dependent and is therefore probably triggered by a DNA damage signal [2].
• Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell death in Drosophila melanogaster [2].
• Loss of maternal 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 [3].
• Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk [4].
• Analysis of the meiotic cell cycle progression shows that the Drosophila Chk2 homolog is not required during early meiotic prophase, as has been observed for Chk2 in C. elegans [4].

Biological context of lok

• By contrast, depletion of Dmnk/DChk2 by RNA interference had little effect on checkpoint responses to hydroxyurea and irradiation [5].
• As Polo-like kinase was shown to colocalize and coimmunoprecipitate with Chk2 [Tsvetkov et al., J. Biol. Chem. 278 (2003) 8468-8475] in mammals, these observations suggest that polo might be a key target of Dmchk2 in regulating mitotic entry in response to DNA damage or replication block [6].
• Drosophila 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. USA 99 (2002) 11305-11310] [6].
• 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 homology to previously identified protein kinases and located at 38B on the second chromosome [7].
• The Dmnk (Drosophila maternal nuclear kinase) gene, encoding a nuclear protein serine/threonine kinase, is expressed predominantly in the germline cells during embryogenesis, suggesting its possible role in the establishment of germ cells [8].

Anatomical context of lok

• At early cleavage-stages Dmnk transcripts are transiently present throughout the embryo, but become restricted to the posterior pole and then to the newly-formed primordial germ cells (pole cells) by the blastoderm stage [7].
• Consistent with mRNA expression, Dmnk proteins in pole cell nuclei are sustained during gastrulation [7].
• Dmnk mRNAs are transcribed in nurse cells and are subsequently localized in the anterior of oocytes during oogenesis, in a manner similar to several maternal transcripts regulating oogenesis and early embryogenesis [7].
• Dmnk proteins become detectable in both somatic and germ line cell nuclei upon their arrival at the periplasm of the syncytial embryo, but then disappear from the somatic cell nuclei [7].

Associations of lok with chemical compounds

• S2 cells display Grp/DChk1-dependent and Dmnk/DChk2-independent cell-cycle-checkpoint activation in response to hydroxyurea and ionizing radiation [5].

Regulatory relationships of lok

• We also show that grp mutant embryos accumulate DNA double-strand breaks and that DNA-damaging agents induce a mnk-dependent block to cellularization and zygotic gene expression [9].

Other interactions of lok

• We propose a novel role for MEI-41 in DSB repair, independent of the Chk1/Chk2-mediated checkpoint response [10].

References