Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation

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Authors

BÁRTA Tomáš VINARSKÝ Vladimír HOLUBCOVÁ Zuzana DOLEŽALOVÁ Dáša VERNER Jan POSPÍŠILOVÁ Šárka DVOŘÁK Petr HAMPL Aleš

Year of publication 2010
Type Article in Periodical
Magazine / Source Stem Cells
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1002/stem.451
Field Genetics and molecular biology
Keywords Human embryonic stem cells; DNA damage; Checkpoint activation; UVC; Cdc25A; p53
Description Embryonic stem cells progress very rapidly through the cell cycle, allowing limited time for cell cycle regulatory circuits that typically function in somatic cells. Mechanisms that inhibit cell cycle progression upon DNA damage are of particular importance, as their malfunction may contribute to the genetic instability observed in human embryonic stem cells (hESCs). In this study, we exposed undifferentiated hESCs to DNA-damaging ultraviolet radiation-C range (UVC) light and examined their progression through the G1/S transition. We show that hESCs irradiated in G1 phase undergo cell cycle arrest before DNA synthesis and exhibit decreased cyclin-dependent kinase two (CDK2) activity. We also show that the phosphatase Cdc25A, which directly activates CDK2, is downregulated in irradiated hESCs through the action of the checkpoint kinases Chk1 and/or Chk2. Importantly, the classical effector of the p53-mediated pathway, protein p21, is not a regulator of G1/S progression in hESCs. Taken together, our data demonstrate that cultured undifferentiated hESCs are capable of preventing entry into S-phase by activating the G1/S checkpoint upon damage to their genetic complement.
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