MDC1 collaborates with TopBP1 in DNA replication checkpoint control
Open accessAbstract
Human TopBP1 is a major player in the control of the DNA replication checkpoint. In this study, we identified MDC1, a key checkpoint protein involved in the cellular response to DNA double-strand breaks, as a TopBP1-associated protein. The specific TopBP1–MDC1 interaction is mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr (SDT) repeats of MDC1. In addition, we demonstrated that TopBP1 accumulation at stalled replication forks is promoted by the H2AX/MDC1 signaling cascade. Moreover, MDC1 is important for ATR-dependent Chk1 activation in response to replication stress. Collectively, our data suggest that MDC1 facilitates several important steps in both cellular DNA damage response and the DNA replication checkpoint.
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H2AX is phosphorylated near ssDNA coated with RPA at stalled replication forks.
“H2AX is phosphorylated at the vicinity of ssDNA coated with RPA at stalled replication forks [49]”
From Gap-filling and bypass at the replication fork are both active mechanisms for tolerance of low-dose ultraviolet-induced DNA damage in the human genome (2014) · cites this paper as [49]
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References 35 · Cited by 118
- Authors
- Wang, J., Gong, Z., & Chen, J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Chen, Junjie
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2011-04-11
- Volume
- 193
- Issue
- 2
- Pages
- 267-273
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3080258
- OpenAlex
- W2155160595
- Cited by
- 118
- References
- 35
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 3 · 2016: 9 · 2015: 15 · 2014: 13 · 2013: 15 · 2012: 7
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH, W81XWH0510470)
- Kræftens Bekæmpelse
- National Institutes of Health (W81XWH, CA- 016672, CA100109)
- University of Texas MD Anderson Cancer Center ((CA016672))
- National Cancer Institute (R01CA100109, CA089239, CA 016672, R01CA089239, CA 092312, R01CA092312, CA100109, P30CA016672)
- 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
- MDC1, TopBP1, DNA replication checkpoint, BRCT domain, H2AX, ATR, Chk1 activation, replication stress, DNA double-strand breaks, DNA damage response, replication fork stalling
- MeSH terms
- Checkpoint Kinase 1, Carrier Proteins, DNA Repair, DNA Replication, DNA-Binding Proteins, Histones, Humans, Nuclear Proteins, Protein Kinases, Signal Transduction, Trans-Activators, Cell Cycle Proteins, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, DNA Breaks, Double-Stranded
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