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Cited by 431DNA Repair MechanismsDNA and Nucleic Acid ChemistryGenomics and Chromatin Dynamics

Replication protein A-mediated recruitment and activation of Rad17 complexes

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Zou, Lee, Liu, Dou, Elledge, Stephen J.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2336100100PMC PMC283506
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Abstract

The human Rad17–Rfc2-5 and Rad9–Rad1–Hus1 complexes play crucial roles in the activation of the ATR-mediated DNA damage and DNA replication stress response pathways. In response to DNA damage, Rad9 is recruited to chromatin in a Rad17-dependent manner in human cells. However, the DNA structures recognized by the Rad17–Rfc2-5 complex during the damage response have not been defined. Here, we show that replication protein A (RPA) stimulates the binding of the Rad17–Rfc2-5 complex to single-stranded DNA (ssDNA), primed ssDNA, and a gapped DNA structure. Furthermore, RPA facilitates the recruitment of the Rad9–Rad1–Hus1 complex by the Rad17–Rfc2-5 complex to primed and gapped DNA structures in vitro . These findings suggest that RPA-coated ssDNA is an important part of the structures recognized by the Rad17–Rfc2-5 complex. Unlike replication factor C (RFC), which uses the 3′ primer/template junction to recruit proliferating cell nuclear antigen (PCNA), the Rad17–Rfc2-5 complex can use both the 5′ and the 3′ primer/template junctions to recruit the Rad9–Rad1–Hus1 complex, and it shows a preference for gapped DNA structures. These results explain how the Rad17–Rfc2-5 complex senses DNA damage and DNA replication stress to initiate checkpoint signaling.

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  • ATR in complex with ATRIP binds RPA-coated single-stranded DNA through an ATRIP-RPA interaction, and ATRIP activates ATR checkpoint kinase activity.

    “ATR in complex with its nuclear binding partner ATR-interacting protein (ATRIP) binds to this RPA-coated ssDNA via an ATRIP-RPA interaction. ATRIP also serves to activate the checkpoint kinase activity of ATR 4, 27–30.”

    From Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation (2017) · cites this paper as [30]

  • ATRIP and Ddc2 directly bind RPA-covered ssDNA, while 9-1-1 loading requires an RFC-like complex that places it at the dsDNA/5′ ssDNA junction.

    “While ATRIP and Ddc2 directly bind RPA-covered ssDNA [44], loading of the 9-1-1 complex requires the activity of an RFC-like complex, that places it at the junction between dsDNA and 5′ ssDNA [45].”

    From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [45]

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  1. [1]Zhou, B. B. & Elledge, S. J. (2000) Nature 408, 433–439. [DOI] [PubMed] [Google Scholar]
  2. [2]Abraham, R. T. (2001) Genes Dev. 15, 2177–2196. [DOI] [PubMed] [Google Scholar]
  3. [3]Zou, L. & Elledge, S. J. (2003) Science 300, 1542–1548. [DOI] [PubMed] [Google Scholar]
  4. [4]Kondo, T., Wakayama, T., Naiki, T., Matsumoto, K. & Sugimoto, K. (2001) Science 294, 867–870. [DOI] [PubMed] [Google Scholar]
  5. [5]Melo, J. A., Cohen, J. & Toczyski, D. P. (2001) Genes Dev. 15, 2809–2821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. [6]Zou, L., Cortez, D. & Elledge, S. J. (2002) Genes Dev. 16, 198–208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. [7]Green, C. M., Erdjument-Bromage, H., Tempst, P. & Lowndes, N. F. (2000) Curr. Biol. 10, 39–42. [DOI] [PubMed] [Google Scholar]
  8. [8]Lindsey-Boltz, L. A., Bermudez, V. P., Hurwitz, J. & Sancar, A. (2001) Proc. Natl. Acad. Sci. USA 98, 11236–11241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. [9]Griffith, J. D., Lindsey-Boltz, L. A. & Sancar, A. (2002) J. Biol. Chem. 277, 15233–15236. [DOI] [PubMed] [Google Scholar]
  10. [10]Tsurimoto, T. & Stillman, B. (1990) Proc. Natl. Acad. Sci. USA 87, 1023–1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. [11]Bermudez, V. P., Lindsey-Boltz, L. A., Cesare, A. J., Maniwa, Y., Griffith, J. D., Hurwitz, J. & Sancar, A. (2003) Proc. Natl. Acad. Sci. USA 100, 1633–1638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. [12]Majka, J. & Burgers, P. M. (2003) Proc. Natl. Acad. Sci. USA 100, 2249–2254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. [13]Waga, S. & Stillman, B. (1998) Mol. Cell. Biol. 18, 4177–4187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. [14]Kim, H. S. & Brill, S. J. (2001) Mol. Cell. Biol. 21, 3725–3737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. [15]Henricksen, L. A., Umbricht, C. B. & Wold, M. S. (1994) J. Biol. Chem. 269, 11121–11132. [PubMed] [Google Scholar]
  16. [16]Umezu, K., Sugawara, N., Chen, C., Haber, J. E. & Kolodner, R. D. (1998) Genetics 148, 989–1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. [17]Pellicioli, A., Lee, S. E., Lucca, C., Foiani, M. & Haber, J. E. (2001) Mol. Cell 7, 293–300. [DOI] [PubMed] [Google Scholar]
  18. [18]Lee, S. E., Moore, J. K., Holmes, A., Umezu, K., Kolodner, R. D. & Haber, J. E. (1998) Cell 94, 399–409. [DOI] [PubMed] [Google Scholar]
  19. [19]Sogo, J. M., Lopes, M. & Foiani, M. (2002) Science 297, 599–602. [DOI] [PubMed] [Google Scholar]
  20. [20]Zhang, G., Gibbs, E., Kelman, Z., O'Donnell, M. & Hurwitz, J. (1999) Proc. Natl. Acad. Sci. USA 96, 1869–1874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. [21]Naiki, T., Shimomura, T., Kondo, T., Matsumoto, K. & Sugimoto, K. (2000) Mol. Cell. Biol. 20, 5888–5896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. [22]Lydall, D. & Weinert, T. (1995) Science 270, 1488–1491. [DOI] [PubMed] [Google Scholar]
  23. [23]Michael, W. M., Ott, R., Fanning, E. & Newport, J. (2000) Science 289, 2133–2137. [DOI] [PubMed] [Google Scholar]
  24. [24]Wood, R. D. (1996) Annu. Rev. Biochem. 65, 135–167. [DOI] [PubMed] [Google Scholar]

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Authors
Zou, L., Liu, D., & Elledge, S. J.
Affiliations
Brigham and Women's Hospital (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-11-06
Volume
100
Issue
24
Pages
13827-13832
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2336100100
PMC
PMC283506
OpenAlex
W2161699458
Cited by
431
References
24
Citations by year
2026: 5 · 2025: 4 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 14 · 2020: 14 · 2019: 6 · 2018: 8 · 2017: 20 · 2016: 16 · 2015: 19 · 2014: 16 · 2013: 19 · 2012: 16
FWCI
10.23
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • Howard Hughes Medical Institute
  • Damon Runyon Cancer Research Foundation
  • National Institutes of Health (GM44664)
  • National Institute of General Medical Sciences (GM-44664, R37GM044664, R01GM044664)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
replication protein A, ATR signaling, DNA damage response, replication stress, single-stranded DNA, DNA damage checkpoint
MeSH terms
DNA Damage, DNA Replication, DNA-Binding Proteins, DNA, Single-Stranded, Humans, Models, Biological, Recombinant Proteins, Saccharomyces cerevisiae, Cell Cycle Proteins, Macromolecular Substances, Replication Protein A, Replication Protein C, In Vitro Techniques

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