ATM/ATR SIGNALING PATHWAY ACTIVATION IN HUMAN EMBRYONIC STEM CELLS AFTER DNA DAMAGE
I.I. Suvorova,1,2,* I.V. Kozhukharova,1 N.N. Nikolsky,1 V.A. Pospelov 1,2
1 Institute of Cytology RAS, St. Petersburg, and 2 St. Petersburg State University;
* e-mail: irsuvorov@yandex.ru
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 γH2AX 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.
Key words: human embryonic stem cells, DNA damage, ATM, ATR, γH2AX, DNA repair
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