title: [ATM/ATR signaling pathway activation in human embryonic stem cells after DNA damage].
abstract: Embryonic stem cells (ESCs) are the progenitors of all adult cells so any disruption in their genome can have disastrous consequences for the developing organism. ESCs are characterized by a high proliferation activity and do not undergo checkpoints upon DNA-damage executing only G2/M delay after DNA damage. ATM and ATR kinase are key sensors of DNA double strands breaks and activate downstream signaling pathways involving checkpoints, DNA repair and apoptosis. We estimated ATM/ATR signaling pathway activation in human ESCs and have revealed that irradiation induced ATM, ATR Chk2 phosphorylation, γH2AX foci formation and their co-localization with 53BP1 and Rad51 proteins. Interestingly, human ESCs display non-induced yH2AX foci co-localized with Rad51 and marking DNA single-strand breaks. Next we have revealed the substantial contribution of ATM, Chk1 and Chk2 kinases to G2/M block after irradiation of human ESCs and ATM-dependent activation (phosphorylation) of p53. However p53 activation and subsequent induction of p21 gene expression after DNA damage do not result in p21 protein accumulation due to proteasomal degradation.
authors.forename: I I
authors.initials: II
authors.lastname: Suvorova
authors.forename: I V
authors.initials: IV
authors.lastname: Kozhukharova
authors.forename: N N
authors.initials: NN
authors.lastname: Nikol'skiĭ
authors.forename: V A
authors.initials: VA
authors.lastname: Pospelov
mesh_terms: D017209:Apoptosis / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C495901:TP53 protein, human; C498301:TP53BP1 protein, human; D016159:Tumor Suppressor Protein p53; D000071857:Tumor Suppressor p53-Binding Protein 1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051135:Rad51 Recombinase