The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase and increases its DNA substrate utilisation efficiency: implications for DNA repair
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In eukaryotic cells, checkpoints are activated in response to DNA damage. This requires the action of DNA damage sensors such as the Rad family proteins. The three human proteins Rad9, Rad1 and Hus1 form a heterotrimeric complex (called the 9-1-1 complex) that is recruited onto DNA upon damage. DNA damage also triggers the recruitment of DNA repair proteins at the lesion, including specialized DNA polymerases. In this work, we showed that the 9-1-1 complex can physically interact with DNA polymerase beta in vitro. Functional analysis revealed that the 9-1-1 complex had a stimulatory effect on DNA polymerase beta activity. However, the presence of 9-1-1 complex neither affected DNA polymerase lambda, another X family DNA polymerase, nor the two replicative DNA polymerases alpha and delta. DNA polymerase beta stimulation resulted from an increase in its affinity for the primer-template and the interaction with the 9-1-1 complex stimulated deoxyribonucleotides misincorporation by DNA polymerase beta. In addition, the 9-1-1 complex enhanced DNA strand displacement synthesis by DNA polymerase beta on a 1 nt gap DNA substrate. Our data raise the possibility that the 9-1-1 complex might attract DNA polymerase beta to DNA damage sites, thus connecting directly checkpoints and DNA repair.
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The 9-1-1 complex interacts with BER proteins APE1, Pol β, FEN1, DNA ligase I, and DNA glycosylases MutY, NEIL1, and TDG, stimulating their DNA repair activities.
“As a critical component of ATR-Chk1 checkpoint pathway, the 9-1-1 complex interacts with several BER proteins: APE1, Polymerase β (Pol β), FEN1, DNA ligase I, as well as DNA glycosylases MutY, NEIL1, and TDG, thereby stimulating their DNA repair activities [177–185] (Fig. 3).”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [177]
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Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Towbin, H., Staehelin, T., & Gordon, J. (1979) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.76.9.4350 · Cited by 51,421 · see citing works
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311 · see citing works
Antibodies, a laboratory manual
(1989) · Biomedicine & Pharmacotherapy · doi:10.1016/0753-3322(89)90130-3 · Cited by 12,318 · see citing works
Ashburner, M. (1989) · Cold Spring Harbor Laboratory eBooks · Cited by 6,739 · see citing works
Antibodies: A laboratory manual
J.L. (1989) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(89)90307-1 · Cited by 5,141 · see citing works
Genome maintenance mechanisms for preventing cancer
Hoeijmakers, J. H. J. (2001) · Nature · doi:10.1038/35077232 · Cited by 3,939 · see citing works
The DNA damage response: putting checkpoints in perspective
Zhou, B.-B. S., & Elledge, S. J. (2000) · Nature · doi:10.1038/35044005 · Cited by 3,213 · see citing works
Proliferating cell nuclear antigen (PCNA): a dancer with many partners
Maga, G., & Hübscher, U. (2003) · Journal of Cell Science · doi:10.1242/jcs.00653 · Cited by 1,093 · see citing works
Hübscher, U., Maga, G., & Spadari, S. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.090501.150041 · Cited by 691 · see citing works
Excision of Deoxyribose Phosphate Residues by DNA Polymerase β During DNA Repair
Matsumoto, Y., & Kim, K. (1995) · Science · doi:10.1126/science.7624801 · Cited by 683 · see citing works
Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatinPreprint
Zou, L., Cortez, D., & Elledge, S. J. (2002) · Genes & Development · doi:10.1101/gad.950302 · Cited by 498 · see citing works
A unified view of the DNA-damage checkpoint
Melo, J. A., & Toczyski, D. P. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00312-5 · Cited by 457 · see citing works
Replication protein A-mediated recruitment and activation of Rad17 complexes
Zou, L., Liu, D., & Elledge, S. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336100100 · Cited by 431 · see citing works
Two checkpoint complexes are independently recruited to sites of DNA damage in vivo
Melo, J. A., Cohen, J., & Toczyski, D. P. (2001) · Genes & Development · doi:10.1101/gad.903501 · Cited by 384 · see citing works
Ellison, V., & Stillman, B. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000033 · Cited by 363 · see citing works
Bermudez, V. P., Lindsey-Boltz, L. A., Cesare, A. J., Maniwa, Y., Griffith, J. D., Hurwitz, J., & Sancar, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437927100 · Cited by 324 · see citing works
Venclovas, Č., & Thelen, M. P. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.13.2481 · Cited by 268 · see citing works
Recruitment of Mec1 and Ddc1 Checkpoint Proteins to Double-Strand Breaks Through Distinct Mechanisms
Kondo, T., Wakayama, T., Naiki, T., Matsumoto, K., & Sugimoto, K. (2001) · Science · doi:10.1126/science.1063827 · Cited by 258 · see citing works
Yeast Rad17/Mec3/Ddc1: A sliding clamp for the DNA damage checkpoint
Majka, J., & Burgers, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437148100 · Cited by 255 · see citing works
Multiple competition reactions for RPA order the assembly of the DNA polymerase δ holoenzyme
Yuzhakov, A., Kelman, Z., Hurwitz, J., & O’Donnell, M. E. (1999) · The EMBO Journal · doi:10.1093/emboj/18.21.6189 · Cited by 212 · see citing works
Purification and characterization of human DNA damage checkpoint Rad complexes
Lindsey‐Boltz, L. A., Bermudez, V. P., Hurwitz, J., & Sancar, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201373498 · Cited by 198 · see citing works
Human DNA Polymerase β Deoxyribose Phosphate Lyase
Prasad, R., Beard, W. A., Strauss, P. R., & Wilson, S. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.24.15263 · Cited by 184 · see citing works
DNA Polymerase λ, a Novel DNA Repair Enzyme in Human Cells
García–Díaz, M., Bębenek, K., Sabariegos, R., Domı́nguez, O., Rodrı́guez, J., Kirchhoff, T., García‐Palomero, E., Picher, Á. J., Juárez, R., Ruiz, J. F., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111601200 · Cited by 184 · see citing works
Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis
Hasan, S., Hassa, P. O., Imhof, R., & Hottiger, M. O. (2001) · Nature · doi:10.1038/35066610 · Cited by 177 · see citing works
Abasic Translesion Synthesis by DNA Polymerase β Violates the “A-rule”
Efrati, E., Tocco, G., Eritja, R., Wilson, S. H., & Goodman, M. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.4.2559 · Cited by 165 · see citing works
Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses
Martinho, R. G., Lindsay, H. D., Flaggs, G., DeMaggio, A. J., Hoekstra, M. F., Carr, A. M., & Bentley, N. J. (1998) · The EMBO Journal · doi:10.1093/emboj/17.24.7239 · Cited by 161 · see citing works
[11] Purification and domain-mapping of mammalian DNA polymerase β
Beard, W. A., & Wilson, S. H. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)62013-3 · Cited by 157 · see citing works
Checkpoint activation regulates mutagenic translesion synthesisPreprint
Kai, M., & Wang, T. S. ‐. (2003) · Genes & Development · doi:10.1101/gad.1043203 · Cited by 157 · see citing works
Burtelow, M. A., Roos‐Mattjus, P., Rauen, M. P., Babendure, J. R., & Karnitz, L. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102946200 · Cited by 142 · see citing works
Depurination-induced infidelity of DNA synthesis with purified DNA replication proteins in vitro
Kunkel, T. A., Schaaper, R. M., & Loeb, L. A. (1983) · Biochemistry · doi:10.1021/bi00279a012 · Cited by 137 · see citing works
Direct Interaction between Mammalian DNA Polymerase β and Proliferating Cell Nuclear Antigen
Kedar, P. S., Kim, S., Robertson, A., Hou, E. W., Prasad, R., Horton, J. K., & Wilson, S. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201497200 · Cited by 127 · see citing works
Reconstitution of Human DNA Polymerase δ Using Recombinant Baculoviruses
Podust, V. N., Chang, L., Ott, R., Dianov, G. L., & Fanning, E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109684200 · Cited by 115 · see citing works
Acetylation Regulates the DNA End-Trimming Activity of DNA Polymerase β
Hasan, S., El‐Andaloussi, N., Hardeland, U., Hassa, P. O., Bürki, C., Imhof, R., Schär, P., & Hottiger, M. O. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00745-1 · Cited by 114 · see citing works
Burtelow, M. A., Kaufmann, S. H., & Karnitz, L. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001244200 · Cited by 114 · see citing works
Griffith, J. D., Lindsey‐Boltz, L. A., & Sancar, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200129200 · Cited by 114 · see citing works
Physical and functional interactions between nucleotide excision repair and DNA damage checkpoint
Giannattasio, M., Lazzaro, F., Longhese, M. P., Plevani, P., & Muzi‐Falconi, M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600051 · Cited by 113 · see citing works
Hoffmann, J., Pillaire, M., Maga, G., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5356 · Cited by 110 · see citing works
Maga, G., Villani, G., Ramadan, K., Shevelev, I., Gac, N. T. L., Blanco, L., Blanca, G., Spadari, S., & Hübscher, U. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206889200 · Cited by 103 · see citing works
Podust, V. N., & Hübscher, U. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.4.841 · Cited by 91 · see citing works
DNA polymerase switching: I. Replication factor C displaces DNA polymerase α prior to PCNA loading
Maga, G., Stucki, M., Spadari, S., & Hübscher, U. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3394 · Cited by 89 · see citing works
Long‐patch DNA repair synthesis during base excision repair in mammalian cells
Sattler, U., Frit, P., Salles, B., & Calsou, P. (2003) · The EMBO Reports · doi:10.1038/sj.embor.embor796 · Cited by 89 · see citing works
Clamp and clamp loader structures of the human checkpoint protein complexes, Rad9‐1‐1 and Rad17‐RFC
Shiomi, Y., Shinozaki, A., Nakada, D., Sugimoto, K., Usukura, J., Obuse, C., & Tsurimoto, T. (2002) · Genes to Cells · doi:10.1046/j.1365-2443.2002.00566.x · Cited by 87 · see citing works
Nuclear factories for signalling and repairing DNA double strand breaks in living fission yeast
Meister, P. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg719 · Cited by 80 · see citing works
The mammalian primase is part of a high molecular weight DNA polymerase alpha polypeptide.
Hübscher, U. (1983) · The EMBO Journal · doi:10.1002/j.1460-2075.1983.tb01394.x · Cited by 75 · see citing works
Roos‐Mattjus, P., Vroman, B. T., Burtelow, M. A., Rauen, M. P., Eapen, A. K., & Karnitz, L. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207272200 · Cited by 75 · see citing works
The delta subunit of Escherichia coli DNA polymerase III holoenzyme is the dnaX gene product.
Hübscher, U., & Kornberg, A. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.12.6284 · Cited by 75 · see citing works
Mossi, R., Keller, R., Ferrari, E. S., et al. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3395 · Cited by 66 · see citing works
A Role for DNA Polymerase β in Mutagenic UV Lesion Bypass
Servant, L., Cazaux, C., Bieth, A., Iwai, S., Hanaoka, F., & Hoffmann, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207101200 · Cited by 61 · see citing works
Structure-Function Analysis of Fission Yeast Hus1-Rad1-Rad9 Checkpoint Complex
Kaur, R., Kostrub, C. F., & Enoch, T. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.12.3744 · Cited by 50 · see citing works
Maga, G., & Hübscher, U. (1995) · Biochemistry · doi:10.1021/bi00003a023 · Cited by 39 · see citing works
Ng, L., McConnell, M., Tan, C. K., et al. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38687-9 · Cited by 32 · see citing works
Cesare, A. J., Griffith, J. D., Bermudez, V. P., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/8z40-9880 · Cited by 30 · see citing works
Maga, G., Jónsson, Z. O., Stucki, M., Spadari, S., & Hübscher, U. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2314 · Cited by 28 · see citing works
Colocalization of human Rad17 and PCNA in late S phase of the cell cycle upon replication block
Dahm, K., & Hübscher, U. (2002) · Oncogene · doi:10.1038/sj.onc.1205872 · Cited by 28 · see citing works
Purification and characterization of human DNA damage checkpoint Rad complexes
Hurwitz, J., Bermudez, V. P., Lindsey‐Boltz, L. A., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/a18w-1111 · Cited by 9 · see citing works
Cotterill, S., & Kearsey, S. E. (2002) · Wiley eBooks · doi:10.1038/npg.els.0001045 · Cited by 8 · see citing works
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Wang, W., Brandt, P., Rossi, M. L., Lindsey-Boltz, L., Podust, V., Fanning, E., Sancar, A., & Bambara, R. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407686101 · Cited by 98 · see citing works
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Friedrich-Heineken, E., Toueille, M., Tännler, B., Bürki, C., Ferrari, E., Hottiger, M. O., & Hübscher, U. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.09.018 · Cited by 76 · see citing works
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Self-citationThe human checkpoint sensor Rad9–Rad1–Hus1 interacts with and stimulates NEIL1 glycosylase
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- Authors
- Toueille, M.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Toueille, M.
- ORCID
- Toueille, M.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-06-21
- Volume
- 32
- Issue
- 11
- Pages
- 3316-3324
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC443528
- OpenAlex
- W1981313684
- Cited by
- 122
- References
- 57
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2020: 1 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 14 · 2012: 6
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Association pour la Recherche sur le Cancer
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31.61361.00, 61361)
- 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
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- 9-1-1 complex, Rad9, RAD1, Hus1, DNA damage checkpoint, DNA polymerase beta, DNA polymerase lambda, DNA repair, misincorporation, strand displacement synthesis, DNA damage sensor
- MeSH terms
- Base Sequence, Deoxyribonucleotides, DNA, DNA Damage, DNA Repair, Exonucleases, Humans, Templates, Genetic, Cell Cycle Proteins, DNA Polymerase beta, Schizosaccharomyces pombe Proteins, Macromolecular Substances
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