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Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation
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SYSNO ASEP 0350028 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation Tvůrce(i) Bárta, Tomáš (UEM-P)
Vinarský, Vladimír (UEM-P)
Holubcová, Z. (CZ)
Doležalová, Dáša (UEM-P)
Verner, J. (CZ)
Pospíšilová, Š. (CZ)
Dvořák, Petr (UEM-P)
Hampl, Aleš (UEM-P)Zdroj.dok. Stem Cells. - : Oxford University Press - ISSN 1066-5099
Roč. 28, č. 7 (2010), s. 1143-1152Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova human embryonic stem cells ; DNA damage ; checkpoint activation Vědní obor RIV EB - Genetika a molekulární biologie CEZ AV0Z50390512 - UEM-P (2005-2011) AV0Z50390703 - UEM-P (2007-2013) UT WOS 000280746400004 DOI 10.1002/stem.451 Anotace 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. Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2011
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