The structural determinants of checkpoint activation
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Here, we demonstrate that primed, single-stranded DNA (ssDNA) is sufficient for activation of the ATR-dependent checkpoint pathway in Xenopus egg extracts. Using this structure, we define the contribution of the 5′- and 3′-primer ends to Chk1 activation when replication is blocked and ongoing. In addition, we show that although ssDNA is not sufficient for checkpoint activation, the amount of ssDNA adjacent to the primer influences the level of Chk1 phosphorylation. These observations define the minimal DNA requirements for checkpoint activation and suggest that primed ssDNA represents a common checkpoint activating-structure formed following many types of damage.
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RPA-coated 5'-primed single-stranded DNA is the determinant DNA structure for ATR activation in response to stalled replication forks or DNA damage.
“5′-primed ssDNA coated with RPA (RPA-ssDNA) is the determinant DNA structure for ATR activation in response to stalled DNA replication forks or DNA damage [41, 94–96].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [96]
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- Authors
- MacDougall, C. A., Byun, T. S., Van, C., Yee, M.-C., & Cimprich, K. A.
- Affiliations
- Stanford University (US)
- Corresponding author
- Cimprich, Karlene A.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-04-15
- Volume
- 21
- Issue
- 8
- Pages
- 898-903
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1847708
- OpenAlex
- W2128322002
- Cited by
- 240
- References
- 37
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 13 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 14 · 2016: 12 · 2015: 15 · 2014: 20 · 2013: 15 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- American Cancer Society
- Leukemia and Lymphoma Society
- National Institutes of Health
- National Institute of General Medical Sciences (GM62193, R01GM062193)
- National Institute of Environmental Health Sciences (R01ES016486)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA damage checkpoint, ATR signaling, Chk1 phosphorylation, single-stranded DNA, DNA replication block, checkpoint activation, Xenopus egg extracts, DNA damage response
- MeSH terms
- Checkpoint Kinase 1, Animals, Cell Cycle, DNA Damage, DNA Replication, DNA, Single-Stranded, Ovum, Phosphorylation, Protein Kinases, Xenopus laevis, S Phase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Xenopus Proteins, Ataxia Telangiectasia Mutated Proteins
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