Interaction of Human DNA Polymerase η with Monoubiquitinated PCNA
Open accessAbstract
Most types of DNA damage block replication fork progression during DNA synthesis because replicative DNA polymerases are unable to accommodate altered DNA bases in their active sites. To overcome this block, eukaryotic cells employ specialized translesion synthesis (TLS) polymerases, which can insert nucleotides opposite damaged bases. In particular, TLS by DNA polymerase eta (poleta) is the major pathway for bypassing UV photoproducts. How the cell switches from replicative to TLS polymerase at the site of blocked forks is unknown. We show that, in human cells, PCNA becomes monoubiquitinated following UV irradiation of the cells and that this is dependent on the hRad18 protein. Monoubiquitinated PCNA but not unmodified PCNA specifically interacts with poleta, and we have identified two motifs in poleta that are involved in this interaction. Our findings provide an attractive mechanism by which monoubiquitination of PCNA might mediate the polymerase switch.
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During translesion synthesis, PCNA is monoubiquitinated at K164 by Rad18, stimulating recruitment of TLS polymerases.
“During translesion synthesis, the PCNA sliding clamp is monoubiquitinated at lysine residue 164 (K164) by the E3 ubiquitin ligase, Rad18 (Watanabe et al., 2004). This modification stimulates recruitment of translesion synthesis polymerases, which bind the PCNA ubiquitin group via their ubiquitin-binding domains (Kannouche et al., 2004; Bienko et al., 2005).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Kannouche et al., 2004
Cites
RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO
Hoege, C., Pfander, B., Moldovan, G., Pyrowolakis, G., & Jentsch, S. (2002) · Nature · doi:10.1038/nature00991 · Cited by 2,202 · see citing works
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., & Hanaoka, F. (1999) · Nature · doi:10.1038/21447 · Cited by 1,292 · see citing works
Protein regulation by monoubiquitin
Hicke, L. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056583 · Cited by 1,213 · see citing works
Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA
Krishna, T. S. R., Kong, X., Gary, S. L., Burgers, P., & Kuriyan, J. (1994) · Cell · doi:10.1016/0092-8674(94)90014-0 · Cited by 902 · see citing works
The Y-Family of DNA Polymerases
Ohmori, H., Friedberg, E. C., Fuchs, R. P., Goodman, M. F., Hanaoka, F., Hinkle, D. C., Kunkel, T. A., Lawrence, C. W., Livneh, Z., Nohmi, T., et al. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00278-7 · Cited by 882 · see citing works
Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation
Stelter, P., & Ulrich, H. D. (2003) · Nature · doi:10.1038/nature01965 · Cited by 849 · see citing works
Hofmann, R. M., & Pickart, C. M. (1999) · Cell · doi:10.1016/s0092-8674(00)80575-9 · Cited by 815 · see citing works
Structure of the C-Terminal Region of p21WAF1/CIP1 Complexed with Human PCNA
Gulbis, J. M., Kelman, Z., Hurwitz, J., O’Donnell, M. E., & Kuriyan, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81347-1 · Cited by 805 · see citing works
Campbell, D. S., & Holt, C. E. (2001) · Neuron · doi:10.1016/s0896-6273(01)00551-7 · Cited by 797 · see citing works
Sequential Assembly of the Nucleotide Excision Repair Factors In Vivo
Volker, M., Moné, M. J., Karmakar, P., van Hoffen, A., Schul, W., Vermeulen, W., Hoeijmakers, J. H. J., DRIEL, R. V., van Zeeland, A. A., & Mullenders, L. H. F. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00281-7 · Cited by 782 · see citing works
<i>hRAD30</i> Mutations in the Variant Form of Xeroderma Pigmentosum
Johnson, R. E., Kondratick, C. M., Prakash, S., & Prakash, L. (1999) · Science · doi:10.1126/science.285.5425.263 · Cited by 732 · see citing works
Rad6-Dependent Ubiquitination of Histone H2B in Yeast
Robzyk, K., Recht, J., & Osley, M. A. (2000) · Science · doi:10.1126/science.287.5452.501 · Cited by 666 · see citing works
Mechanisms of accurate translesion synthesis by human DNA polymerase η
Masutani, C., Kusumoto, R., Iwai, S., & Hanaoka, F. (2000) · The EMBO Journal · doi:10.1093/emboj/19.12.3100 · Cited by 504 · see citing works
Two RING finger proteins mediate cooperation between ubiquitin‐conjugating enzymes in DNA repair
Ulrich, H. D., & Jentsch, S. (2000) · The EMBO Journal · doi:10.1093/emboj/19.13.3388 · Cited by 427 · see citing works
Structure of the Catalytic Core of S. cerevisiae DNA Polymerase η
Trincão, J., Johnson, R. E., Escalante, C. R., Prakash, S., Prakash, L., & Aggarwal, A. K. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00306-9 · Cited by 344 · see citing works
Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier.
Tomlinson, G. E., Chen, T. T., Stastny, V., Virmani, A. K., Spillman, M. A., Tonk, V. S., Blum, J. L., Schneider, N. R., Wistuba, I. I., Shay, J. W., et al. (1998) · PubMed · Cited by 292 · see citing works
Bailly, V., Lauder, S., Prakash, S., & Prakash, L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.37.23360 · Cited by 292 · see citing works
A ubiquitin‐binding motif required for intramolecular monoubiquitylation, the CUE domain
Shih, S. C., Prag, G., Francis, S. A., Sutanto, M. A., Hurley, J. H., & Hicke, L. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg140 · Cited by 283 · see citing works
Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains
Mallery, D. L., Vandenberg, C. J., & Hiom, K. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf691 · Cited by 280 · see citing works
Kannouche, P., Broughton, B. C., Volker, M., Hanaoka, F., Mullenders, L. H. F., & Lehmann, A. R. (2001) · Genes & Development · doi:10.1101/gad.187501 · Cited by 278 · see citing works
Self-citationStructural and functional conservation of two human homologs of the yeast DNA repair gene RAD6.
Koken, M. H. M., Reynolds, P. R., Jaspers-Dekker, I., Prakash, L., Prakash, S., Bootsma, D., & Hoeijmakers, J. H. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.20.8865 · Cited by 263 · see citing works
Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity
McCulloch, S. D., Kokoska, R. J., Masutani, C., Iwai, S., Hanaoka, F., & Kunkel, T. A. (2004) · Nature · doi:10.1038/nature02352 · Cited by 246 · see citing works
Solution Structure of a CUE-Ubiquitin Complex Reveals a Conserved Mode of Ubiquitin Binding
Kang, R. S.-O., Daniels, C. M., Francis, S. A., Shih, S. C., Salerno, W. J., Hicke, L., & Radhakrishnan, I. (2003) · Cell · doi:10.1016/s0092-8674(03)00362-3 · Cited by 237 · see citing works
Physical and Functional Interactions of Human DNA Polymerase η with PCNA
Haracska, L., Johnson, R. E., Unk, I., Phillips, B., Hurwitz, J., Prakash, L., & Prakash, S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.21.7199-7206.2001 · Cited by 235 · see citing works
Mechanism of Ubiquitin Recognition by the CUE Domain of Vps9p
Prag, G., Misra, S., Jones, E., Ghirlando, R., Davies, B. A., Horazdovsky, B. F., & Hurley, J. H. (2003) · Cell · doi:10.1016/s0092-8674(03)00364-7 · Cited by 230 · see citing works
Structural basis for recruitment of translesion DNA polymerase Pol IV/DinB to the β‐clamp
Bunting, K. A., Roe, S. M., & Pearl, L. H. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg568 · Cited by 225 · see citing works
Tateishi, S., Sakuraba, Y., Masuyama, S., Inoue, H., & Yamaizumi, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.14.7927 · Cited by 140 · see citing works
Closing the gaps among a web of DNA repair disorders
Michelson, R. J., & Weinert, T. A. (2000) · BioEssays · doi:10.1002/1521-1878(200011)22:11 · Cited by 61 · see citing works
The effects of ionizing radiation on DNA synthesis in eukaryotic cells
Rowley, R. B. (1999) · International Journal of Radiation Biology · doi:10.1080/095530099140456 · Cited by 22 · see citing works
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PCNA, the Maestro of the Replication Fork
Moldovan, G.-L., Pfander, B., & Jentsch, S. (2007) · Cell · doi:10.1016/j.cell.2007.05.003 · Cited by 1,796 · see citing works
Regulation of DNA repair throughout the cell cycle
Branzei, D., & Foiani, M. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2351 · Cited by 1,228 · see citing works
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Huyen, Y., Zgheib, O., DiTullio Jr, R. A., Gorgoulis, V. G., Zacharatos, P., Petty, T. J., Sheston, E. A., Mellert, H. S., Stavridi, E. S., & Halazonetis, T. D. (2004) · Nature · doi:10.1038/nature03114 · Cited by 884 · see citing works
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Branzei, D., & Foiani, M. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2852 · Cited by 786 · see citing works
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Bienko, M., Green, C. M., Crosetto, N., Rudolf, F., Zapart, G., Coull, B., Kannouche, P., Wider, G., Peter, M., Lehmann, A. R., et al. (2005) · Science · doi:10.1126/science.1120615 · Cited by 712 · see citing works
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Sale, J. E., Lehmann, A. R., & Woodgate, R. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3289 · Cited by 665 · see citing works
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Wang, W. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2159 · Cited by 663 · see citing works
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Waters, L. S., Minesinger, B. K., Wiltrout, M. E., D'Souza, S., Woodruff, R. V., & Walker, G. C. (2009) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00034-08 · Cited by 591 · see citing works
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Ogi, T., Limsirichaikul, S., Overmeer, R. M., Volker, M., Takenaka, K., Cloney, R., Nakazawa, Y., Niimi, A., Miki, Y., Jaspers, N. G., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.02.009 · Cited by 392 · see citing works
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LEHMANN, A., NIIMI, A., OGI, T., BROWN, S., SABBIONEDA, S., WING, J., KANNOUCHE, P., & GREEN, C. (2007) · DNA Repair · doi:10.1016/j.dnarep.2007.02.003 · Cited by 389 · see citing works
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Patil, M., Pabla, N., & Dong, Z. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1307-3 · Cited by 317 · see citing works
Motegi, A., Liaw, H.-J., Lee, K.-Y., Roest, H. P., Maas, A., Wu, X., Moinova, H., Markowitz, S. D., Ding, H., Hoeijmakers, J. H. J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805685105 · Cited by 304 · see citing works
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Llano, M., Vanegas, M., Hutchins, N., Thompson, D., Delgado, S., & Poeschla, E. M. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.04.073 · Cited by 199 · see citing works
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“This modification stimulates recruitment of translesion synthesis polymerases, which bind the PCNA ubiquitin group via their ubiquitin-binding domains (Kannouche et al., 2004; Bienko et al., 2005).”
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Vrouwe, M. G., Pines, A., Overmeer, R. M., Hanada, K., & Mullenders, L. H. F. (2011) · Journal of Cell Science · doi:10.1242/jcs.075325 · Cited by 100 · see citing works
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Soria, G., Speroni, J., Podhajcer, O. L., Prives, C., & Gottifredi, V. (2008) · Journal of Cell Science · doi:10.1242/jcs.027730 · Cited by 94 · see citing works
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Sabbioneda, S., Bortolomai, I., Giannattasio, M., Plevani, P., & Muzi-Falconi, M. (2007) · DNA Repair · doi:10.1016/j.dnarep.2006.09.002 · Cited by 65 · see citing works
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- Authors
- Kannouche, P. L., Wing, J., & Lehmann, A. R.
- Affiliations
- University of Sussex (GB)
- Corresponding author
- Lehmann, Alan R
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 14
- Issue
- 4
- Pages
- 491-500
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1840855988
- Cited by
- 845
- References
- 29
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 28 · 2023: 21 · 2022: 21 · 2021: 29 · 2020: 28 · 2019: 17 · 2018: 34 · 2017: 32 · 2016: 34 · 2015: 33 · 2014: 39 · 2013: 38 · 2012: 62
- FWCI
- 21.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3364 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mauritius Research Council (EU FP5 QoL, QLG-CT-1999-00181)
- 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 › DNA and Nucleic Acid Chemistry
- Keywords
- DNA polymerase eta, PCNA monoubiquitination, translesion synthesis, UV photoproducts, replication fork stalling, protein-protein interaction, DNA damage tolerance, UV-induced DNA damage
- MeSH terms
- Y-Family DNA Polymerases, Chromatin, DNA, DNA Damage, DNA-Directed DNA Polymerase, DNA Replication, DNA-Binding Proteins, Humans, Ultraviolet Rays, Protein Structure, Tertiary, Proliferating Cell Nuclear Antigen, Ubiquitin, Ubiquitin-Protein Ligases
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