Related Experiment Video
Updated: Apr 19, 2026

Study of the DNA Damage Checkpoint using Xenopus Egg Extracts
Published on: November 5, 2012
[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.
Related Concept Videos
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
The Intrinsic Apoptotic Pathway
Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
MAPK Signaling Cascades

