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1.
Mol Cell Biochem ; 356(1-2): 209-16, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21761203

RESUMO

CK2 is a highly conserved serine-threonine kinase involved in biological processes such as embryonic development, circadian rhythms, inflammation, and cancer. Biochemical experiments have implicated CK2 in the control of several cellular processes and in the regulation of signal transduction pathways. Our laboratory is interested in characterizing the cellular, signaling, and molecular mechanisms regulated by CK2 during early embryonic development. For this purpose, animal models, including mice deficient in CK2 genes, are indispensable tools. Using CK2α gene-deficient mice, we have recently shown that CK2α is a critical regulator of mid-gestational morphogenetic processes, as CK2α deficiency results in defects in heart, brain, pharyngeal arch, tail bud, limb bud, and somite formation. Morphogenetic processes depend upon the precise coordination of essential cellular processes in which CK2 has been implicated, such as proliferation and survival. Here, we summarize the overall phenotype found in CK2α (-/- ) mice and describe our initial analysis aimed to identify the cellular processes affected in CK2α mutants.


Assuntos
Caseína Quinase II/metabolismo , Desenvolvimento Embrionário , Morfogênese , Animais , Apoptose , Caseína Quinase II/deficiência , Proliferação de Células , Embrião de Mamíferos/anatomia & histologia , Embrião de Mamíferos/citologia , Embrião de Mamíferos/enzimologia , Cabeça/embriologia , Botões de Extremidades/embriologia , Camundongos , Fenótipo , Somitos/citologia , Somitos/enzimologia , Cauda/embriologia
2.
Nucleic Acids Res ; 30(21): 4740-50, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12409465

RESUMO

Proton nuclear magnetic resonance (NMR) spectroscopy is employed to characterize the kinetics of base-pair opening in a series of 9mer duplexes containing different single base mismatches. The imino protons from the different mismatched, as well as fully matched, duplexes are assigned from the imino-imino region in the WATERGATE NOESY spectra. The exchange kinetics of the imino protons are measured from selective longitudinal relaxation times. In the limit of infinite exchange catalyst concentration, the exchange times of the mismatch imino protons extrapolate to much shorter lifetimes than are commonly observed for an isolated GC base pair. Different mismatches exhibit different orders of base-pair lifetimes, e.g. a TT mismatch has a shorter base-pair lifetime than a GG mismatch. The effect of the mismatch was observed up to a distance of two neighboring base pairs. This indicates that disruption in the duplex caused by the mismatch is quite localized. The overall order of base-pair lifetimes in the selected sequence context of the base pair is GC > GG > AA > CC > AT > TT. Interestingly, the fully matched AT base pair has a shorter base-pair lifetime relative to many of the mismatches. Thus, in any given base pair, the exchange lifetime can exhibit a strong dependence on sequence context. These findings may be relevant to the way mismatch recognition is accomplished by proteins and small molecules.


Assuntos
Pareamento Incorreto de Bases/genética , Pareamento de Bases , Espectroscopia de Ressonância Magnética , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/metabolismo , Sequência de Bases , Ligação de Hidrogênio , Cinética , Desnaturação de Ácido Nucleico , Oligodesoxirribonucleotídeos/genética , Mutação Puntual/genética , Prótons , Temperatura
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