Redox-sensitive alteration of replisome architecture safeguards genome integrity

Research output: Contribution to journalJournal articleResearchpeer-review

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Redox-sensitive alteration of replisome architecture safeguards genome integrity. / Somyajit, Kumar; Gupta, Rajat; Sedlackova, Hana; Neelsen, Kai John; Ochs, Fena; Rask, Maj-Britt; Choudhary, Chunaram; Lukas, Jiri.

In: Science, Vol. 358, No. 6364, 10.11.2017, p. 797-802.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Somyajit, K, Gupta, R, Sedlackova, H, Neelsen, KJ, Ochs, F, Rask, M-B, Choudhary, C & Lukas, J 2017, 'Redox-sensitive alteration of replisome architecture safeguards genome integrity', Science, vol. 358, no. 6364, pp. 797-802. https://doi.org/10.1126/science.aao3172

APA

Somyajit, K., Gupta, R., Sedlackova, H., Neelsen, K. J., Ochs, F., Rask, M-B., ... Lukas, J. (2017). Redox-sensitive alteration of replisome architecture safeguards genome integrity. Science, 358(6364), 797-802. https://doi.org/10.1126/science.aao3172

Vancouver

Somyajit K, Gupta R, Sedlackova H, Neelsen KJ, Ochs F, Rask M-B et al. Redox-sensitive alteration of replisome architecture safeguards genome integrity. Science. 2017 Nov 10;358(6364):797-802. https://doi.org/10.1126/science.aao3172

Author

Somyajit, Kumar ; Gupta, Rajat ; Sedlackova, Hana ; Neelsen, Kai John ; Ochs, Fena ; Rask, Maj-Britt ; Choudhary, Chunaram ; Lukas, Jiri. / Redox-sensitive alteration of replisome architecture safeguards genome integrity. In: Science. 2017 ; Vol. 358, No. 6364. pp. 797-802.

Bibtex

@article{c148dd3f345945d58f1fd85877f2ebef,
title = "Redox-sensitive alteration of replisome architecture safeguards genome integrity",
abstract = "DNA replication requires coordination between replication fork progression and deoxynucleotide triphosphate (dNTP)-generating metabolic pathways. We find that perturbation of ribonucleotide reductase (RNR) in humans elevates reactive oxygen species (ROS) that are detected by peroxiredoxin 2 (PRDX2). In the oligomeric state, PRDX2 forms a replisome-associated ROS sensor, which binds the fork accelerator TIMELESS when exposed to low levels of ROS. Elevated ROS levels generated by RNR attenuation disrupt oligomerized PRDX2 to smaller subunits, whose dissociation from chromatin enforces the displacement of TIMELESS from the replisome. This process instantly slows replication fork progression, which mitigates pathological consequences of replication stress. Thus, redox signaling couples fluctuations of dNTP biogenesis with replisome activity to reduce stress during genome duplication. We propose that cancer cells exploit this pathway to increase their adaptability to adverse metabolic conditions.",
author = "Kumar Somyajit and Rajat Gupta and Hana Sedlackova and Neelsen, {Kai John} and Fena Ochs and Maj-Britt Rask and Chunaram Choudhary and Jiri Lukas",
note = "Copyright {\circledC} 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
year = "2017",
month = "11",
day = "10",
doi = "10.1126/science.aao3172",
language = "English",
volume = "358",
pages = "797--802",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6364",

}

RIS

TY - JOUR

T1 - Redox-sensitive alteration of replisome architecture safeguards genome integrity

AU - Somyajit, Kumar

AU - Gupta, Rajat

AU - Sedlackova, Hana

AU - Neelsen, Kai John

AU - Ochs, Fena

AU - Rask, Maj-Britt

AU - Choudhary, Chunaram

AU - Lukas, Jiri

N1 - Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2017/11/10

Y1 - 2017/11/10

N2 - DNA replication requires coordination between replication fork progression and deoxynucleotide triphosphate (dNTP)-generating metabolic pathways. We find that perturbation of ribonucleotide reductase (RNR) in humans elevates reactive oxygen species (ROS) that are detected by peroxiredoxin 2 (PRDX2). In the oligomeric state, PRDX2 forms a replisome-associated ROS sensor, which binds the fork accelerator TIMELESS when exposed to low levels of ROS. Elevated ROS levels generated by RNR attenuation disrupt oligomerized PRDX2 to smaller subunits, whose dissociation from chromatin enforces the displacement of TIMELESS from the replisome. This process instantly slows replication fork progression, which mitigates pathological consequences of replication stress. Thus, redox signaling couples fluctuations of dNTP biogenesis with replisome activity to reduce stress during genome duplication. We propose that cancer cells exploit this pathway to increase their adaptability to adverse metabolic conditions.

AB - DNA replication requires coordination between replication fork progression and deoxynucleotide triphosphate (dNTP)-generating metabolic pathways. We find that perturbation of ribonucleotide reductase (RNR) in humans elevates reactive oxygen species (ROS) that are detected by peroxiredoxin 2 (PRDX2). In the oligomeric state, PRDX2 forms a replisome-associated ROS sensor, which binds the fork accelerator TIMELESS when exposed to low levels of ROS. Elevated ROS levels generated by RNR attenuation disrupt oligomerized PRDX2 to smaller subunits, whose dissociation from chromatin enforces the displacement of TIMELESS from the replisome. This process instantly slows replication fork progression, which mitigates pathological consequences of replication stress. Thus, redox signaling couples fluctuations of dNTP biogenesis with replisome activity to reduce stress during genome duplication. We propose that cancer cells exploit this pathway to increase their adaptability to adverse metabolic conditions.

U2 - 10.1126/science.aao3172

DO - 10.1126/science.aao3172

M3 - Journal article

C2 - 29123070

VL - 358

SP - 797

EP - 802

JO - Science

JF - Science

SN - 0036-8075

IS - 6364

ER -

ID: 186152687