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Cited by 103DNA Repair MechanismsCytokine Signaling Pathways and InteractionsCancer-related Molecular Pathways

STAT3 modulates the DNA damage response pathway

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Barry, Seán P., Townsend, Paul A., Knight, Richard A., Scarabelli, Tiziano M., Latchman, David S., Stephanou, Anastasis·2010·International Journal of Experimental Pathology
DOI 10.1111/j.1365-2613.2010.00734.xPMC PMC3010549
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Abstract

Summary: The STAT3 transcription factor is well known to function as an anti‐apoptotic factor, especially in numerous malignancies. Recently we showed that STAT3 is cytoprotective and that cells lacking STAT3 are more sensitive to oxidative stress. A key feature of oxidative stress involves activation of the DNA damage pathway. However, a role for STAT3 or its contribution in response to DNA damage has not been described. In the present study we show that cells lacking STAT3 are less efficient in repairing damaged DNA. Moreover, STAT3 deficient cells show reduced activity of the ATM‐Chk2 and ATR‐Chk1 pathways, both important pathways in sensing DNA damage. Finally we show that MDC1, a regulator of the ATM‐Chk2 pathway and facilitator of the DNA damage response, is modulated by STAT3 at the transcriptional level. These findings demonstrate that STAT3 is necessary for efficient repair of damaged DNA, partly by modulating the ATM‐Chk2 and ATR‐Chk1 pathways.

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Crossref · 10.1111/j.1365-2613.2010.00734.x

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  • STAT3 is activated by UV through DNA damage and reactive oxygen species.

    “STAT3 also is activated by UV through DNA damage and reactive oxygen species (Shen et al., 2001; Aziz et al., 2007a; Barry et al., 2010; Bito et al., 2010b).”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Barry et al., 2010

    The Abstract (page unavailable) reports STAT3 activation in rat myocardium after ischemia–reperfusion injury, which generates reactive oxygen species. The Results and Abstract link STAT3 to repair of UV-damaged DNA, but do not show that UV activates STAT3 through DNA damage or reactive oxygen species. (LLM, conf=0.81)

    Experimental — accuracy not yet measured

  • Persistently elevated pY-STAT3 levels mediated by chronic UV exposure are a key step in UV-induced skin cancer.

    “persistently elevated pY-STAT3 levels mediated by chronic UV exposure are a key step in UV-induced skin cancer (Chan et al., 2004a,b; Aziz et al., 2007a,b; Barry et al., 2010).”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Barry et al., 2010

    The Results report that STAT3 levels correlate with repair of UV-damaged DNA in mouse embryonic fibroblasts, and the Discussion considers a possible role for elevated STAT3 in cancer-cell DNA repair (page numbers unavailable). The paper does not establish that chronic UV exposure persistently elevates pY-STAT3 or that this is a key step in UV-induced skin cancer. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • STAT3 transcriptionally regulates mediator of DNA damage checkpoint 1, the master regulator of the ATM-chk2 pathway.

    “STAT3 transcriptionally regulates mediator of DNA damage checkpoint 1, the master regulator of the ATM-chk2 pathway (Barry et al., 2010).”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Barry et al., 2010

    The Abstract and Discussion (page not specified) state that STAT3 modulates MDC1 expression at the transcriptional level and that MDC1 is a regulator of the ATM–Chk2 pathway. They call MDC1 a key mediator, not the singular “master regulator”; the Results instead identify ATM as the pathway’s apical kinase. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Cells lacking STAT3 are less efficient in repairing damaged DNA due to reduced activity of ATM-Chk2 and ATR-Chk1.

    “cells lacking STAT3 are less efficient in repairing damaged DNA due to reduced activity of ataxia-telangiectasia mutated (ATM)-Chk2 and ATM and RAD3‐related (ATR)-Chk1, two major pathways involved in sensing DNA damage (Barry et al., 2010).”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Barry et al., 2010

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Cites

Flagged first, then by citations

Research works printed but not linked: 26

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Sorted by citations

Authors
Barry, S. P., Townsend, P. A., Knight, R. A., Scarabelli, T. M., Latchman, D. S., & Stephanou, A.
Affiliations
  • University College London (GB)
  • Southampton General Hospital (GB)
  • Wayne State University (US)
Corresponding author
Stephanou, Anastasis
ORCID
Venue
International Journal of Experimental Pathology
Publisher
Wiley
Published
2010-08-27
Volume
91
Issue
6
Pages
506-514
ISSN
  • 0959-9673 (ISSN-L)
  • 1365-2613
DOI
10.1111/j.1365-2613.2010.00734.x
PMC
PMC3010549
OpenAlex
W1792389549
Cited by
103
References
2
Citations by year
2026: 4 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 4 · 2017: 8 · 2016: 8 · 2015: 3 · 2014: 7 · 2013: 2 · 2012: 6
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • International Journal of Experimental Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
British Heart Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
STAT3, DNA damage response, DNA repair, ATM-Chk2 pathway, ATR-Chk1 pathway, MDC1, oxidative stress, transcriptional regulation, cytoprotection, apoptosis
MeSH terms
Checkpoint Kinase 1, Animals, Cell Line, Cell Survival, Cells, Cultured, DNA Damage, DNA Repair, DNA-Binding Proteins, Flow Cytometry, Humans, Protein Kinases, Blotting, Western, Signal Transduction, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, STAT3 Transcription Factor, Mice, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2

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