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Chk1 and Claspin potentiate PCNA ubiquitination
Open accessAbstract
Chk1 is a kinase crucial for genomic integrity and an effector of ATR (ATM and Rad3-realated) in DNA damage response. Here, we show that Chk1 regulates the DNA damage-induced ubiquitination of proliferating cell nuclear antigen (PCNA), which facilitates the continuous replication of damaged DNA. Surprisingly, this Chk1 function requires the DNA replication protein Claspin but not ATR. Claspin, which is stabilized by Chk1, regulates the binding of the ubiquitin ligase Rad18 to chromatin. Timeless, a Claspin-associating protein, is also required for efficient PCNA ubiquitination. Thus, Chk1 and the Claspin–Timeless module of replication forks not only participate in ATR signaling, but also protect stressed forks independently of ATR.
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“activated Chk1 phosphorylates its own substrates such as protein Rad51, which is involved in the DSB repair by HR [193–195]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [194]
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Metadata
- Authors
- Yang, X. H., Shiotani, B., Classon, M., & Zou, L.
- Affiliations
- Harvard University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-05-01
- Volume
- 22
- Issue
- 9
- Pages
- 1147-1152
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2335311
- OpenAlex
- W2156915836
- Cited by
- 111
- References
- 35
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 15 · 2012: 11
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Susan G. Komen for the Cure
- Breast Cancer Alliance
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM076388, GM076388)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Chk1, Claspin, PCNA ubiquitination, ATR signaling, DNA damage response, TIMELESS, replication fork, replication stress, genome stability
- MeSH terms
- Checkpoint Kinase 1, DNA Replication, HeLa Cells, Humans, Hydroxyurea, Morpholines, Plasmids, Protein Kinases, Pyrones, Transfection, Ultraviolet Rays, Blotting, Western, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Proliferating Cell Nuclear Antigen, RNA, Small Interfering, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Ubiquitination, Ataxia Telangiectasia Mutated Proteins
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