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

0350028 - ÚEM 2011 RIV US eng J - Journal Article
Bárta, Tomáš - Vinarský, Vladimír - Holubcová, Z. - Doležalová, Dáša - Verner, J. - Pospíšilová, Š. - Dvořák, Petr - Hampl, Aleš
Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation.
Stem Cells. Roč. 28, č. 7 (2010), s. 1143-1152. ISSN 1066-5099. E-ISSN 1549-4918
Grant - others:GA MŠk(CZ) 1M0538; GA MZd(CZ) NS10439; GA MŠk(CZ) MUNIE/E/0118/2009; EC FP6(XE) LSHG-CT-2006-018739
Program: 1M
Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703
Keywords : human embryonic stem cells * DNA damage * checkpoint activation
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 7.871, year: 2010
http://arl-repository.lib.cas.cz/uloziste_av/UEM-P/cav_un_epca-0350028_01.pdf

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). This study shows that under a low dose of DNA damaging UVC light, hESCs respond by activating classical G1/S checkpoint molecules to prevent entry into S phase with unrepaired DNA. This G1 block in hESCs is mediated by Chk1 and Chk2, which phosphorylate Cdc25A, thereby marking it for degradation. Lack of CDK-activating Cdc25A results in low CDK2 activity, without contribution from the p53-p21 pathway. 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.
Permanent Link: http://hdl.handle.net/11104/0190130