Stimulation of human DNA polymerase epsilon by MDM2

Asahara, H.

doi:10.1093/nar/gkg342

Cited by 33DNA Repair MechanismsCancer-related Molecular PathwaysDNA and Nucleic Acid Chemistry

Stimulation of human DNA polymerase epsilon by MDM2

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Asahara, H.·2003·Nucleic Acids Research

DOI 10.1093/nar/gkg342PMC PMC154228

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Abstract

The human DNA polymerase epsilon catalytic subunit consists of a 140-kDa N-terminal domain that contains the catalytic activity and a 120-kDa C-terminal domain that binds to the other subunits and to exogenous peptides, including PCNA and MDM2. We report here that recombinant human MDM2 purified from insect cells or Escherichia coli stimulated the activity of DNA polymerase epsilon up to 10- and 40-fold, respectively, but not those of DNA polymerase beta or Klenow fragment of E.coli DNA polymerase I. Kinetic studies indicated that MDM2 increased the maximum velocity of the reaction, but did not change substrate affinities. The stimulation depended upon the interaction of the N-terminal 166 amino acid residues of MDM2 with the C-terminal domain of the full-length catalytic subunit, since the deletion of 166 amino acids from N-terminal of MDM2 or the removal of the C-terminal domain of DNA polymerase epsilon by trypsin digestion or competition for binding to it by the addition of excess C-terminal fragment eliminated the stimulation. Since DNA polymerase epsilon appears to be involved in DNA replication, recombination and repair synthesis, we suggest that MDM2 binding to DNA polymerase epsilon might be part of a reconfiguration process that allows DNA polymerase epsilon to associate with repair/recombination proteins in response to DNA damage.

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A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506 · see citing works
Amplification of a gene encoding a p53-associated protein in human sarcomas
Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B. (1992) · Nature · doi:10.1038/358080a0 · Cited by 1,949 · see citing works
The p53-mdm-2 autoregulatory feedback loop.
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1126 · Cited by 1,801 · see citing works
Mammalian DNA nucleotide excision repair reconstituted with purified protein components
Aboussekhra, A., Biggerstaff, M., Shivji, M. K. K., Vilpo, J. A., Moncollin, V., Podust, V. N., Protić, M., Hübscher, U., Egly, J.-M., & Wood, R. D. (1995) · Cell · doi:10.1016/0092-8674(95)90289-9 · Cited by 837 · see citing works
ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage
Maya, R., Balass, M., Kim, S.-T., Shkedy, D., Leal, J.-F. M., Shifman, O., Moas, M., Buschmann, T., Ronai, Z., Shiloh, Y., et al. (2001) · Genes & Development · doi:10.1101/gad.886901 · Cited by 716 · see citing works
Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line.
Fakharzadeh, S. S., Trusko, S. P., & George, D. L. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07676.x · Cited by 704 · see citing works
Mapping of the p53 and mdm-2 Interaction Domains
Chen, J., Maréchal, V., & Levine, A. J. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4107 · Cited by 689 · see citing works
Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein
Martin, K., Trouche, D., Hagemeier, C., Sørensen, T. S., Thangue, N. B. L., & Kouzarides, T. (1995) · Nature · doi:10.1038/375691a0 · Cited by 454 · see citing works
DNA polymerase ϵ links the DNA replication machinery to the S phase checkpoint
Navas, T. A., Zhou, Z. Y., & Elledge, S. J. (1995) · Cell · doi:10.1016/0092-8674(95)90448-4 · Cited by 403 · see citing works
The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth.
Finlay, C. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.1.301 · Cited by 311 · see citing works
Nucleotide Excision Repair DNA Synthesis by DNA Polymerase .epsilon. in the Presence of PCNA, RFC, and RPA
Shivji, M. K. K., Podust, V. N., Hübscher, U., & Wood, R. D. (1995) · Biochemistry · doi:10.1021/bi00015a012 · Cited by 279 · see citing works
DNA Polymerase ε Catalytic Domains Are Dispensable for DNA Replication, DNA Repair, and Cell Viability
Kesti, T., Flick, K. M., Keränen, S., Syväoja, J. E., & Wittenberg, C. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80361-5 · Cited by 276 · see citing works
Repression of p53-mediated transcription by MDM2: a dual mechanism
Thut, C. J., Goodrich, J. A., & Tjian, R. (1997) · Genes & Development · doi:10.1101/gad.11.15.1974 · Cited by 272 · see citing works
Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: Transforming ability and frequent detection in human cancer
Sigalas, I., Calvert, A. H., Anderson, J. J., Neal, D. E., & Lunec, J. (1996) · Nature Medicine · doi:10.1038/nm0896-912 · Cited by 268 · see citing works
Mapping of the p53 and mdm-2 Interaction Domains
Chen, J., Maréchal, V., & Levine, A. J. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4107-4114.1993 · Cited by 247 · see citing works
DNA repair synthesis in human fibroblasts requires DNA polymerase delta.
Nishida, C., Reinhard, P., & Linn, S. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)57421-x · Cited by 240 · see citing works
Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53.
Lundgren, K., Montes de Oca Luna, R., McNeill, Y. B., Emerick, E. P., Spencer, B., Barfield, C. R., Lozano, G., Rosenberg, M. P., & Finlay, C. A. (1997) · Genes & Development · doi:10.1101/gad.11.6.714 · Cited by 235 · see citing works
HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone‐fold proteins
Poot, R. A., Dellaire, G., Hülsmann, B. B., Grimaldi, M. A., Corona, D. F. V., Becker, P. B., Bickmore, W. A., & Varga‐Weisz, P. (2000) · The EMBO Journal · doi:10.1093/emboj/19.13.3377 · Cited by 220 · see citing works
Analysis of the Essential Functions of the C-terminal Protein/Protein Interaction Domain of Saccharomyces cerevisiae pol ε and Its Unexpected Ability to Support Growth in the Absence of the DNA Polymerase Domain
Dua, R., Levy, D. L., & Campbell, J. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.32.22283 · Cited by 200 · see citing works
DNA-dependent DNA polymerases from HeLa cell nuclei II. Template and substrate utilization
Schlabach, A. J., Fridlender, B. R., Bolden, A. H., & Weissbach, A. (1971) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(71)90793-5 · Cited by 194 · see citing works
RAD9 and DNA polymerase epsilon form parallel sensory branches for transducing the DNA damage checkpoint signal in Saccharomyces cerevisiae.Preprint
Navas, T. A., Sánchez, Y., & Elledge, S. J. (1996) · Genes & Development · doi:10.1101/gad.10.20.2632 · Cited by 167 · see citing works
Purification and characterization of two new high molecular weight forms of DNA polymerase .delta.
Crute, J. J., Wahl, A. F., & Bambara, R. A. (1986) · Biochemistry · doi:10.1021/bi00349a005 · Cited by 151 · see citing works
Characterization of a large form of DNA polymerase δ from HeLa cells that is insensitive to proliferating cell nuclear antigen
Syväoja, J. E., & Linn, S. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81640-x · Cited by 143 · see citing works
The Mdm2 Oncoprotein Interacts with the Cell Fate Regulator Numb
Juven‐Gershon, T., Shifman, O., Unger, T., Elkeles, A., Haupt, Y., & Oren, M. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.3974 · Cited by 136 · see citing works
Decreased fidelity of DNA polymerase activity isolated from aging human fibroblasts.
Linn, S., Kairis, M., & Holliday, R. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.8.2818 · Cited by 132 · see citing works
A mammalian protein complex that repairs double-strand breaks and deletions by recombination
Jessberger, R., Podust, V. N., Hübscher, U., & Berg, P. R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82439-5 · Cited by 129 · see citing works
DNA polymerase epsilon may be dispensable for SV40‐ but not cellular‐DNA replication.
Zlotkin, T., Kaufmann, G., Jiang, Y. Q., Lee, M. Y., Uitto, L., Syväoja, J. E., Dornreiter, I., Fanning, E., & Nethanel, T. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00583.x · Cited by 115 · see citing works
CloningDPB3, the gene encoding the third subunit of DNA polymerase II ofSaccharomyces cerevisiae
Araki, H., Hamatake, R. K., Morrison, A., et al. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.18.4867 · Cited by 104 · see citing works
Analysis of the degradation function of Mdm2.
Kubbutat, M. H. G., Ludwig, R., Levine, A. J., & Vousden, K. H. (1999) · PubMed · Cited by 102 · see citing works
DNA Polymerases δ and ε are Required for Chromosomal Replication in Saccharomyces cerevisiae
Budd, M. E., & Campbell, J. L. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.1.496-505.1993 · Cited by 99 · see citing works
The DNA Polymerase Domain of polε Is Required for Rapid, Efficient, and Highly Accurate Chromosomal DNA Replication, Telomere Length Maintenance, and Normal Cell Senescence inSaccharomyces cerevisiae
Ohya, T., Kawasaki, Y., Hiraga, S., Kanbara, S., Nakajo, K., Nakashima, N., Suzuki, A., & Sugino, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111573200 · Cited by 92 · see citing works
Nucleotide-excision repair of DNA in cell-free extracts of the yeast Saccharomyces cerevisiae.
Wang, Z., Wu, X., & Friedberg, E. C. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.11.4907 · Cited by 89 · see citing works
Role of the Putative Zinc Finger Domain of Saccharomyces cerevisiae DNA Polymerase ε in DNA Replication and the S/M Checkpoint Pathway
Dua, R., Levy, D. L., & Campbell, J. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.30046 · Cited by 89 · see citing works
Identification and Cloning of Two Histone Fold Motif-containing Subunits of HeLa DNA Polymerase ε
Li, Y., Pursell, Z. F., & Linn, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002548200 · Cited by 88 · see citing works
Human DNA Polymerase ε Colocalizes with Proliferating Cell Nuclear Antigen and DNA Replication Late, but Not Early, in S Phase
Fuss, J. O., & Linn, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110615200 · Cited by 87 · see citing works
Structure and function of the fourth subunit (Dpb4p) of DNA polymerase varepsilon in Saccharomyces cerevisiae
Ohya, T. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.20.3846 · Cited by 84 · see citing works
The mdm-2 Oncogene Can Overcome Wild-Type p53 Suppression of Transformed Cell Growth
Finlay, C. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.1.301-306.1993 · Cited by 83 · see citing works
Schizosaccharomyces pombe cdc 20 + encodes DNA polymerase ɛ and is required for chromosomal replication but not for the S phase checkpoint
D’Urso, G., & Nurse, P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12491 · Cited by 81 · see citing works
A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway
Marchetti, M. A., Kumar, S., Hartsuiker, E., Maftahi, M., Carr, A. M., Freyer, G. A., Burhans, W. C., & Huberman, J. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112702399 · Cited by 73 · see citing works
DNA polymerase ɛ is required for coordinated and efficient chromosomal DNA replication in Xenopus egg extracts
Shou, W.-G., Masuda, T., Takisawa, H., & Sugino, A. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.081088798 · Cited by 60 · see citing works
The Tumor Suppressor p53 and the Oncoprotein Simian Virus 40 T Antigen Bind to Overlapping Domains on the MDM2 Protein
Brown, D. R., Deb, S., Muñoz, R. M., Subler, M. A., & Deb, S. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.11.6849 · Cited by 58 · see citing works
Purification, cDNA Cloning, and Gene Mapping of the Small Subunit of Human DNA Polymerase ε
Li, Y., Asahara, H., Patel, V. S., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.51.32337 · Cited by 50 · see citing works
Self-citation
Subunit Interactions within the Saccharomyces cerevisiae DNA Polymerase ε (pol ε) Complex
Dua, R., Edwards, S., Levy, D. L., & Campbell, J. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002376200 · Cited by 47 · see citing works
A neutralizing antibody against human DNA polymerase epsilon inhibits cellular but not SV40 DNA replication
Pospiech, H. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.19.3799 · Cited by 47 · see citing works
Identification and tryptic cleavage of the catalytic core of HeLa and calf thymus DNA polymerase epsilon.
Kesti, T., & Syväoja, J. E. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)38123-7 · Cited by 42 · see citing works
MDM2 interacts with the C-terminus of the catalytic subunit of DNA polymerase varepsilon
Vlatković, N. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.18.3581 · Cited by 40 · see citing works
Analysis of the mammalian recombination protein complex RC-1
Jessberger, R., Chui, G., Linn, S., & Kemper, B. (1996) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(95)00106-9 · Cited by 28 · see citing works
Overproduction of MDM2 in vivo disrupts S phase independent of E2F1.
Reinke, V., Bortner, D. M., Amelse, L. L., Lundgren, K., Rosenberg, M. P., Finlay, C. A., & Lozano, G. (1999) · PubMed · Cited by 25 · see citing works
Proteolysis of the human DNA polymerase varepsilon catalytic subunit by caspase-3 and calpain specifically during apoptosis
Liu, W. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.21.4180 · Cited by 22 · see citing works
The Tumor Suppressor p53 and the Oncoprotein Simian Virus 40 T Antigen Bind to Overlapping Domains on the MDM2 Protein
Brown, D. R., Deb, S., Muñoz, R. M., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.11.6849-6857.1993 · Cited by 22 · see citing works
Histone and histone fold sequences and structures: a database
Baxevanis, A. D., & Landsman, D. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.1.272 · Cited by 13 · see citing works

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Authors: Asahara, H.
Affiliations: University of California, Berkeley (US)
Corresponding author: Asahara, H.
Venue: Nucleic Acids Research
Publisher: Oxford University Press (OUP)
Published: 2003-05-01
Volume: 31
Issue: 9
Pages: 2451-2459
ISSN: 0305-1048 (ISSN-L)
1362-4962
DOI: 10.1093/nar/gkg342
PMC: PMC154228
OpenAlex: W1945473077
Cited by: 33
References: 52
Citations by year: 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2017: 1 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 5
FWCI: 1.15
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)
Funders: National Institutes of Health (5r01gm030415-17, 5r29ca070165-06)
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council
National Cancer Institute (1R29CA70165)
National Institute of General Medical Sciences (1R01GM30415, R01GM059424, 1R01 GM 59424)
National Institute of Environmental Health Sciences (P30-ES08196)
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 › DNA and Nucleic Acid Chemistry
Keywords: DNA polymerase epsilon, MDM2, enzyme activation, catalytic subunit, C-terminal domain, N-terminal domain, PCNA, DNA replication, DNA repair, recombination, DNA damage response, protein-protein interaction, polymerase kinetics
MeSH terms: Animals, Cell Line, DNA Polymerase II, Enzyme Activation, HeLa Cells, Humans, Kinetics, Nuclear Proteins, Peptide Fragments, Protein Binding, Proto-Oncogene Proteins, Recombinant Proteins, Substrate Specificity, Spodoptera, Proto-Oncogene Proteins c-mdm2

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Stimulation of human DNA polymerase epsilon by MDM2

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