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@article{905275, author = {Bárta, Tomáš and Vinarský, Vladimír and Holubcová, Zuzana and Doležalová, Dáša and Verner, Jan and Pospíšilová, Šárka and Dvořák, Petr and Hampl, Aleš}, article_number = {7}, doi = {http://dx.doi.org/10.1002/stem.451}, keywords = {Human embryonic stem cells; DNA damage; Checkpoint activation; UVC; Cdc25A; p53}, language = {eng}, issn = {1066-5099}, journal = {Stem Cells}, note = {podpora z projektu EU LSHG-CT-2006-018739}, title = {Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation}, volume = {28}, year = {2010} }
TY - JOUR ID - 905275 AU - Bárta, Tomáš - Vinarský, Vladimír - Holubcová, Zuzana - Doležalová, Dáša - Verner, Jan - Pospíšilová, Šárka - Dvořák, Petr - Hampl, Aleš PY - 2010 TI - Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation JF - Stem Cells VL - 28 IS - 7 SP - 1143-1152 EP - 1143-1152 SN - 10665099 N1 - podpora z projektu EU LSHG-CT-2006-018739 KW - Human embryonic stem cells KW - DNA damage KW - Checkpoint activation KW - UVC KW - Cdc25A KW - p53 N2 - 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. ER -
BÁRTA, Tomáš, Vladimír VINARSKÝ, Zuzana HOLUBCOVÁ, Dáša DOLEŽALOVÁ, Jan VERNER, Šárka POSPÍŠILOVÁ, Petr DVOŘÁK a Aleš HAMPL. Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation. \textit{Stem Cells}. 2010, roč.~28, č.~7, s.~1143-1152. ISSN~1066-5099. Dostupné z: https://dx.doi.org/10.1002/stem.451.
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