Initiating Cellular Stress Responses
Open accessAbstract
The phosphoinositide 3-kinase related kinases (PIKKs) mediate responses to diverse stresses, including DNA double-strand breaks (DSBs), abnormal replication fork progression, the recognition of premature termination codons in mRNAs, and inadequate nutrient availability. Rigorous control of these kinases limits cellular damage and promotes cell viability in the presence of stress. Control mechanisms include the localization of PIKKs into multiprotein complexes at the sites of damage and mediation of protein-protein contacts such that substrates are allowed access to the PIKK catalytic domains.
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In response to double-strand breaks, ATM autophosphorylates serine 1981, which causes dimer dissociation into monomers and full ATM activation.
“However, in response to DSBs, ATM auto-phosphorylates Serine 1981, leading to dimer dissociation into a monomer and the full activation of ATM [50, 51].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [50]
In normal conditions ATM is inactive as a dimer or higher-order oligomer, with its kinase domain blocked by a region around serine 1981.
“Under normal conditions, ATM is inactive in a dimer or higher-order oligomer status, when its kinase domain is bound by a region surrounding a critical Serine 1981 and prevented from activation.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [50]
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- Authors
- Bakkenist, C. J., & Kastan, M. B.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Kastan, Michael B
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 118
- Issue
- 1
- Pages
- 9-17
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2010895845
- Cited by
- 544
- References
- 55
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 14 · 2017: 19 · 2016: 17 · 2015: 18 · 2014: 17 · 2013: 23 · 2012: 21
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3303 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- PIKKs, cellular stress response, DNA double-strand breaks, replication fork stalling, nutrient deprivation, protein-protein interaction, protein complexes, kinase localization, DNA damage response
- MeSH terms
- Animals, Cell Survival, DNA Damage, DNA Replication, DNA-Binding Proteins, Enzyme Activation, Humans, Models, Biological, Stress, Physiological, Substrate Specificity, Protein Structure, Tertiary, Phosphatidylinositol 3-Kinases, Catalytic Domain
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