A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells

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Standard

A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. / Ahuja, Akshay K.; Jodkowska, Karolina; Teloni, Federico; Bizard, Anna H.; Zellweger, Ralph; Herrador, Raquel; Ortega, Sagrario; Hickson, Ian D.; Altmeyer, Matthias; Mendez, Juan; Lopes, Massimo.

I: Nature Communications, Bind 7, 10660, 02.2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Ahuja, AK, Jodkowska, K, Teloni, F, Bizard, AH, Zellweger, R, Herrador, R, Ortega, S, Hickson, ID, Altmeyer, M, Mendez, J & Lopes, M 2016, 'A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells', Nature Communications, bind 7, 10660. https://doi.org/10.1038/ncomms10660

APA

Ahuja, A. K., Jodkowska, K., Teloni, F., Bizard, A. H., Zellweger, R., Herrador, R., Ortega, S., Hickson, I. D., Altmeyer, M., Mendez, J., & Lopes, M. (2016). A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. Nature Communications, 7, [10660]. https://doi.org/10.1038/ncomms10660

Vancouver

Ahuja AK, Jodkowska K, Teloni F, Bizard AH, Zellweger R, Herrador R o.a. A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. Nature Communications. 2016 feb.;7. 10660. https://doi.org/10.1038/ncomms10660

Author

Ahuja, Akshay K. ; Jodkowska, Karolina ; Teloni, Federico ; Bizard, Anna H. ; Zellweger, Ralph ; Herrador, Raquel ; Ortega, Sagrario ; Hickson, Ian D. ; Altmeyer, Matthias ; Mendez, Juan ; Lopes, Massimo. / A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. I: Nature Communications. 2016 ; Bind 7.

Bibtex

@article{391499ab3d414f3890a90c0e004708f2,
title = "A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells",
abstract = "Embryonic stem cells (ESCs) represent a transient biological state, where pluripotency is coupled with fast proliferation. ESCs display a constitutively active DNA damage response (DDR), but its molecular determinants have remained elusive. Here we show in cultured ESCs and mouse embryos that H2AX phosphorylation is dependent on Ataxia telangiectasia and Rad3 related (ATR) and is associated with chromatin loading of the ssDNA-binding proteins RPA and RAD51. Single-molecule analysis of replication intermediates reveals massive ssDNA gap accumulation, reduced fork speed and frequent fork reversal. All these marks of replication stress do not impair the mitotic process and are rapidly lost at differentiation onset. Delaying the G1/S transition in ESCs allows formation of 53BP1 nuclear bodies and suppresses ssDNA accumulation, fork slowing and reversal in the following S-phase. Genetic inactivation of fork slowing and reversal leads to chromosomal breakage in unperturbed ESCs. We propose that rapid cell cycle progression makes ESCs dependent on effective replication-coupled mechanisms to protect genome integrity.",
author = "Ahuja, {Akshay K.} and Karolina Jodkowska and Federico Teloni and Bizard, {Anna H.} and Ralph Zellweger and Raquel Herrador and Sagrario Ortega and Hickson, {Ian D.} and Matthias Altmeyer and Juan Mendez and Massimo Lopes",
year = "2016",
month = feb,
doi = "10.1038/ncomms10660",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells

AU - Ahuja, Akshay K.

AU - Jodkowska, Karolina

AU - Teloni, Federico

AU - Bizard, Anna H.

AU - Zellweger, Ralph

AU - Herrador, Raquel

AU - Ortega, Sagrario

AU - Hickson, Ian D.

AU - Altmeyer, Matthias

AU - Mendez, Juan

AU - Lopes, Massimo

PY - 2016/2

Y1 - 2016/2

N2 - Embryonic stem cells (ESCs) represent a transient biological state, where pluripotency is coupled with fast proliferation. ESCs display a constitutively active DNA damage response (DDR), but its molecular determinants have remained elusive. Here we show in cultured ESCs and mouse embryos that H2AX phosphorylation is dependent on Ataxia telangiectasia and Rad3 related (ATR) and is associated with chromatin loading of the ssDNA-binding proteins RPA and RAD51. Single-molecule analysis of replication intermediates reveals massive ssDNA gap accumulation, reduced fork speed and frequent fork reversal. All these marks of replication stress do not impair the mitotic process and are rapidly lost at differentiation onset. Delaying the G1/S transition in ESCs allows formation of 53BP1 nuclear bodies and suppresses ssDNA accumulation, fork slowing and reversal in the following S-phase. Genetic inactivation of fork slowing and reversal leads to chromosomal breakage in unperturbed ESCs. We propose that rapid cell cycle progression makes ESCs dependent on effective replication-coupled mechanisms to protect genome integrity.

AB - Embryonic stem cells (ESCs) represent a transient biological state, where pluripotency is coupled with fast proliferation. ESCs display a constitutively active DNA damage response (DDR), but its molecular determinants have remained elusive. Here we show in cultured ESCs and mouse embryos that H2AX phosphorylation is dependent on Ataxia telangiectasia and Rad3 related (ATR) and is associated with chromatin loading of the ssDNA-binding proteins RPA and RAD51. Single-molecule analysis of replication intermediates reveals massive ssDNA gap accumulation, reduced fork speed and frequent fork reversal. All these marks of replication stress do not impair the mitotic process and are rapidly lost at differentiation onset. Delaying the G1/S transition in ESCs allows formation of 53BP1 nuclear bodies and suppresses ssDNA accumulation, fork slowing and reversal in the following S-phase. Genetic inactivation of fork slowing and reversal leads to chromosomal breakage in unperturbed ESCs. We propose that rapid cell cycle progression makes ESCs dependent on effective replication-coupled mechanisms to protect genome integrity.

U2 - 10.1038/ncomms10660

DO - 10.1038/ncomms10660

M3 - Journal article

C2 - 26876348

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 10660

ER -

ID: 167480205