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MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks

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MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks. / Montales, Katrina; Ruis, Kenna; Lindsay, Howard et al.

In: PLoS ONE, Vol. 17, No. 8, e0271905, 02.08.2022.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Montales, K, Ruis, K, Lindsay, H, Michael, WM & Lustig, AJ (ed.) 2022, 'MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks', PLoS ONE, vol. 17, no. 8, e0271905. https://doi.org/10.1371/journal.pone.0271905

APA

Montales, K., Ruis, K., Lindsay, H., Michael, W. M., & Lustig, A. J. (Ed.) (2022). MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks. PLoS ONE, 17(8), [e0271905]. https://doi.org/10.1371/journal.pone.0271905

Vancouver

Montales K, Ruis K, Lindsay H, Michael WM, Lustig AJ, (ed.). MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks. PLoS ONE. 2022 Aug 2;17(8):e0271905. doi: 10.1371/journal.pone.0271905

Author

Montales, Katrina ; Ruis, Kenna ; Lindsay, Howard et al. / MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks. In: PLoS ONE. 2022 ; Vol. 17, No. 8.

Bibtex

@article{fd10de69e29940a190effc3e26c2c247,
title = "MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks",
abstract = "Ataxia Telangiectasia mutated and RAD3-related (ATR) kinase is activated by DNA replication stress and also by various forms of DNA damage, including DNA double-strand breaks (DSBs). Recruitment to sites of damage is insufficient for ATR activation as one of two known ATR activators, either topoisomerase II-binding protein (TOPBP1) or Ewing{\textquoteright}s tumor-associated antigen 1, must also be present for signaling to initiate. Here, we employ our recently established DSB-mediated ATR activation in Xenopus egg extract (DMAX) system to examine how TOPBP1 is recruited to DSBs, so that it may activate ATR. We report that TOPBP1 is only transiently present at DSBs, with a half-life of less than 10 minutes. We also examined the relationship between TOPBP1 and the MRE11-RAD50-NBS1 (MRN), CtBP interacting protein (CtIP), and Ataxia Telangiectasia mutated (ATM) network of proteins. Loss of MRN prevents CtIP recruitment to DSBs, and partially inhibits TOPBP1 recruitment. Loss of CtIP has no impact on either MRN or TOPBP1 recruitment. Loss of ATM kinase activity prevents CtIP recruitment and enhances MRN and TOPBP1 recruitment. These findings demonstrate that there are MRN-dependent and independent pathways that recruit TOPBP1 to DSBs for ATR activation. Lastly, we find that both the 9-1-1 complex and MDC1 are dispensable for TOPBP1 recruitment to DSBs.",
keywords = "Research Article, Research and analysis methods, Biology and life sciences",
author = "Katrina Montales and Kenna Ruis and Howard Lindsay and Michael, {W. Matthew} and Lustig, {Arthur J.}",
year = "2022",
month = aug,
day = "2",
doi = "10.1371/journal.pone.0271905",
language = "English",
volume = "17",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - MRN-dependent and independent pathways for recruitment of TOPBP1 to DNA double-strand breaks

AU - Montales, Katrina

AU - Ruis, Kenna

AU - Lindsay, Howard

AU - Michael, W. Matthew

A2 - Lustig, Arthur J.

PY - 2022/8/2

Y1 - 2022/8/2

N2 - Ataxia Telangiectasia mutated and RAD3-related (ATR) kinase is activated by DNA replication stress and also by various forms of DNA damage, including DNA double-strand breaks (DSBs). Recruitment to sites of damage is insufficient for ATR activation as one of two known ATR activators, either topoisomerase II-binding protein (TOPBP1) or Ewing’s tumor-associated antigen 1, must also be present for signaling to initiate. Here, we employ our recently established DSB-mediated ATR activation in Xenopus egg extract (DMAX) system to examine how TOPBP1 is recruited to DSBs, so that it may activate ATR. We report that TOPBP1 is only transiently present at DSBs, with a half-life of less than 10 minutes. We also examined the relationship between TOPBP1 and the MRE11-RAD50-NBS1 (MRN), CtBP interacting protein (CtIP), and Ataxia Telangiectasia mutated (ATM) network of proteins. Loss of MRN prevents CtIP recruitment to DSBs, and partially inhibits TOPBP1 recruitment. Loss of CtIP has no impact on either MRN or TOPBP1 recruitment. Loss of ATM kinase activity prevents CtIP recruitment and enhances MRN and TOPBP1 recruitment. These findings demonstrate that there are MRN-dependent and independent pathways that recruit TOPBP1 to DSBs for ATR activation. Lastly, we find that both the 9-1-1 complex and MDC1 are dispensable for TOPBP1 recruitment to DSBs.

AB - Ataxia Telangiectasia mutated and RAD3-related (ATR) kinase is activated by DNA replication stress and also by various forms of DNA damage, including DNA double-strand breaks (DSBs). Recruitment to sites of damage is insufficient for ATR activation as one of two known ATR activators, either topoisomerase II-binding protein (TOPBP1) or Ewing’s tumor-associated antigen 1, must also be present for signaling to initiate. Here, we employ our recently established DSB-mediated ATR activation in Xenopus egg extract (DMAX) system to examine how TOPBP1 is recruited to DSBs, so that it may activate ATR. We report that TOPBP1 is only transiently present at DSBs, with a half-life of less than 10 minutes. We also examined the relationship between TOPBP1 and the MRE11-RAD50-NBS1 (MRN), CtBP interacting protein (CtIP), and Ataxia Telangiectasia mutated (ATM) network of proteins. Loss of MRN prevents CtIP recruitment to DSBs, and partially inhibits TOPBP1 recruitment. Loss of CtIP has no impact on either MRN or TOPBP1 recruitment. Loss of ATM kinase activity prevents CtIP recruitment and enhances MRN and TOPBP1 recruitment. These findings demonstrate that there are MRN-dependent and independent pathways that recruit TOPBP1 to DSBs for ATR activation. Lastly, we find that both the 9-1-1 complex and MDC1 are dispensable for TOPBP1 recruitment to DSBs.

KW - Research Article

KW - Research and analysis methods

KW - Biology and life sciences

U2 - 10.1371/journal.pone.0271905

DO - 10.1371/journal.pone.0271905

M3 - Journal article

VL - 17

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 8

M1 - e0271905

ER -