2026-07-21T14:37:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/109882024-11-29T20:47:34Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Atashpaz, Sina
author
Samadi Shams, Sara
author
Gonzalez, Javier Martin
author
Sebestyén, Endre
author
Arghavanifard, Negar
author
Gnocchi, Andrea
author
Albers, Eliene
author
Minardi, Simone
author
Faga, Giovanni
author
Soffientini, Paolo
author
Allievi, Elisa
author
Cancila, Valeria
author
Bachi, Angela
author
Tripodo, Claudio
author
Ferrari, Francesco
author
López-Contreras, Andrés Joaquin
author
Costanzo, Vincenzo
author
Fernandez-Capetillo, Oscar
funder
Italian Association for Cancer Research
funder
Giovanni Armenise-Harvard Foundation
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Danish Cancer Society
funder
Det Frie Forskningsrad (DFF)
funder
Danish National Research Foundation
2020-09-08T08:56:27Z
2020-09-08T08:56:27Z
2020-03-12
Elife. 2020;9:e54756.
10.7554/eLife.54756
2050-084X
eLife
32163370
http://hdl.handle.net/20.500.12105/10988
Unrepaired DNA damage during embryonic development can be potentially inherited by a large population of cells. However, the quality control mechanisms that minimize the contribution of damaged cells to developing embryos remain poorly understood. Here, we uncovered an ATR- and CHK1-mediated transcriptional response to replication stress (RS) in mouse embryonic stem cells (ESCs) that induces genes expressed in totipotent two-cell (2C) stage embryos and 2C-like cells. This response is mediated by Dux, a multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals. In response to RS, DUX triggers the transcription of 2C-like markers such as murine endogenous retrovirus-like elements (MERVL) and Zscan4. This response can also be elicited by ETAA1-mediated ATR activation in the absence of RS. ATR-mediated activation of DUX requires GRSF1-dependent post-transcriptional regulation of Dux mRNA. Strikingly, activation of ATR expands ESCs fate potential by extending their contribution to both embryonic and extra-embryonic tissues. These findings define a novel ATR dependent pathway involved in maintaining genome stability in developing embryos by controlling ESCs fate in response to RS.
eng
DNA-DAMAGE
EPIGENETIC RESTRICTION
TELOMERE ELONGATION
GENOMIC STABILITY
GENE ATR
ATR expands embryonic stem cell fate potential in response to replication stress.
journal article
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URL
https://repisalud.isciii.es/bitstreams/d0d53740-02ba-43ad-a863-2e3233b883b8/download
File
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application/pdf
ATRexpandsembryonicstemcell_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/bee30508-726b-45be-9e7f-6ecc1285c509/download
File
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text/plain
ATRexpandsembryonicstemcell_2020.pdf.txt