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

BÁRTA, Tomáš, Vladimír VINARSKÝ, Zuzana HOLUBCOVÁ, Dáša DOLEŽALOVÁ, Jan VERNER, Šárka POSPÍŠILOVÁ, Petr DVOŘÁK and Aleš HAMPL. Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation. Stem Cells. 2010, vol. 28, No 7, p. 1143-1152. ISSN 1066-5099. Available from: https://dx.doi.org/10.1002/stem.451.

Basic information

• Original name: Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation
• Authors: BÁRTA, Tomáš (203 Czech Republic, guarantor, belonging to the institution), Vladimír VINARSKÝ (203 Czech Republic, belonging to the institution), Zuzana HOLUBCOVÁ (203 Czech Republic, belonging to the institution), Dáša DOLEŽALOVÁ (703 Slovakia, belonging to the institution), Jan VERNER (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Petr DVOŘÁK (203 Czech Republic, belonging to the institution) and Aleš HAMPL (203 Czech Republic, belonging to the institution).
• Edition: Stem Cells, 2010, 1066-5099.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: Genetics and molecular biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 7.871
• RIV identification code: RIV/00216224:14110/10:00067228
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1002/stem.451
• UT WoS: 000280746400004
• Keywords in English: Human embryonic stem cells; DNA damage; Checkpoint activation; UVC; Cdc25A; p53

Abstract

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.

Links

• MSM0021622430, plan (intention): Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies

• MUNI/E/0118/2009, interní kód MU: Name: Úloha CDK1 v řízení buněčného cyklu lidských embryonálních kmenových buněk.

Investor: Masaryk University, Category E - development project + specific research