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Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage. / Fletcher, Sally C.; Grou, Claudia P.; Legrand, Arnaud J. et al.

In: Nucleic Acids Research, Vol. 46, No. 4, 28.02.2018, p. 1834-1846.

Research output: Contribution to journal › Article › peer-review

Harvard

Fletcher, SC, Grou, CP, Legrand, AJ, Chen, X, Soderstrom, K, Poletto, M & Dianov, GL 2018, 'Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage', Nucleic Acids Research, vol. 46, no. 4, pp. 1834-1846. https://doi.org/10.1093/nar/gkx1291

APA

Fletcher, S. C., Grou, C. P., Legrand, A. J., Chen, X., Soderstrom, K., Poletto, M., & Dianov, G. L. (2018). Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage. Nucleic Acids Research, 46(4), 1834-1846. https://doi.org/10.1093/nar/gkx1291

Vancouver

Fletcher SC, Grou CP, Legrand AJ, Chen X, Soderstrom K, Poletto M et al. Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage. Nucleic Acids Research. 2018 Feb 28;46(4):1834-1846. doi: 10.1093/nar/gkx1291

Author

Fletcher, Sally C. ; Grou, Claudia P. ; Legrand, Arnaud J. et al. / Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage. In: Nucleic Acids Research. 2018 ; Vol. 46, No. 4. pp. 1834-1846.

BibTeX

@article{1a42f6cadd134a40a35c64bdf529762a,
title = "Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage",
abstract = "ATM (ataxia-telangiectasia mutated) is a central molecule for DNA quality control. Its activation by DNA damage promotes cell-cycle delay, which facilitates DNA repair prior to replication. On the other hand, persistent DNA damage has been implicated in ATM-dependent cell death via apoptosis; however, the mechanisms underlying this process remain elusive. Here we find that, in response to persistent DNA strand breaks, ATM phosphorylates transcription factor Sp1 and initiates its degradation.We show that Sp1 controls expression of the key base excision repair gene XRCC1, essential for DNA strand break repair. Therefore, degradation of Sp1 leads to a vicious cycle that involves suppression of DNA repair and further aggravation of the load of DNA damage. This activates transcription of pro-apoptotic genes and renders cells susceptible to elimination via both apoptosis and natural killer cells. These findings constitute a previously unrecognized 'gatekeeper' function of ATM as a detector of cells with persistent DNA damage.",
author = "Fletcher, {Sally C.} and Grou, {Claudia P.} and Legrand, {Arnaud J.} and Xin Chen and Kalle Soderstrom and Mattia Poletto and Dianov, {Grigory L.}",
year = "2018",
month = feb,
day = "28",
doi = "10.1093/nar/gkx1291",
language = "English",
volume = "46",
pages = "1834--1846",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage

AU - Fletcher, Sally C.

AU - Grou, Claudia P.

AU - Legrand, Arnaud J.

AU - Chen, Xin

AU - Soderstrom, Kalle

AU - Poletto, Mattia

AU - Dianov, Grigory L.

PY - 2018/2/28

Y1 - 2018/2/28

N2 - ATM (ataxia-telangiectasia mutated) is a central molecule for DNA quality control. Its activation by DNA damage promotes cell-cycle delay, which facilitates DNA repair prior to replication. On the other hand, persistent DNA damage has been implicated in ATM-dependent cell death via apoptosis; however, the mechanisms underlying this process remain elusive. Here we find that, in response to persistent DNA strand breaks, ATM phosphorylates transcription factor Sp1 and initiates its degradation.We show that Sp1 controls expression of the key base excision repair gene XRCC1, essential for DNA strand break repair. Therefore, degradation of Sp1 leads to a vicious cycle that involves suppression of DNA repair and further aggravation of the load of DNA damage. This activates transcription of pro-apoptotic genes and renders cells susceptible to elimination via both apoptosis and natural killer cells. These findings constitute a previously unrecognized 'gatekeeper' function of ATM as a detector of cells with persistent DNA damage.

AB - ATM (ataxia-telangiectasia mutated) is a central molecule for DNA quality control. Its activation by DNA damage promotes cell-cycle delay, which facilitates DNA repair prior to replication. On the other hand, persistent DNA damage has been implicated in ATM-dependent cell death via apoptosis; however, the mechanisms underlying this process remain elusive. Here we find that, in response to persistent DNA strand breaks, ATM phosphorylates transcription factor Sp1 and initiates its degradation.We show that Sp1 controls expression of the key base excision repair gene XRCC1, essential for DNA strand break repair. Therefore, degradation of Sp1 leads to a vicious cycle that involves suppression of DNA repair and further aggravation of the load of DNA damage. This activates transcription of pro-apoptotic genes and renders cells susceptible to elimination via both apoptosis and natural killer cells. These findings constitute a previously unrecognized 'gatekeeper' function of ATM as a detector of cells with persistent DNA damage.

UR - http://www.scopus.com/inward/record.url?scp=85042907434&partnerID=8YFLogxK

U2 - 10.1093/nar/gkx1291

DO - 10.1093/nar/gkx1291

M3 - Article

C2 - 29294106

AN - SCOPUS:85042907434

VL - 46

SP - 1834

EP - 1846

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 4

ER -

ID: 14279985