Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis.
Open accessAbstract
Translesion synthesis (TLS) is the major pathway by which mammalian cells replicate across DNA lesions. Upon DNA damage, ubiquitination of proliferating cell nuclear antigen (PCNA) induces bypass of the lesion by directing the replication machinery into the TLS pathway. Yet, how this modification is recognized and interpreted in the cell remains unclear. Here we describe the identification of two ubiquitin (Ub)–binding domains (UBM and UBZ), which are evolutionarily conserved in all Y-family TLS polymerases (pols). These domains are required for binding of polη and polι to ubiquitin, their accumulation in replication factories, and their interaction with monoubiquitinated PCNA. Moreover, the UBZ domain of polη is essential to efficiently restore a normal response to ultraviolet irradiation in xeroderma pigmentosum variant (XP-V) fibroblasts. Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 Bienko et al., 2005
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
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
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
Interaction of Human DNA Polymerase η with Monoubiquitinated PCNA
Kannouche, P. L., Wing, J., & Lehmann, A. R. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00259-x · Cited by 845 · see citing works
Self-citationHicke, L., Schubert, H., & Hill, C. P. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1701 · Cited by 795 · see citing works
Ubiquitylation and cell signaling
Haglund, K., & Đikić, I. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600808 · Cited by 736 · see citing works
Watanabe, K., Tateishi, S., Kawasuji, M., Tsurimoto, T., Inoue, H., & Yamaizumi, M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600383 · Cited by 538 · see citing works
Hofmann, K., & Falquet, L. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01835-7 · Cited by 449 · see citing works
Self-citationThe UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway
Hofmann, K., & Bücher, P. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)30015-7 · Cited by 404 · see citing works
Self-citationTrading Places: How Do DNA Polymerases Switch during Translesion DNA Synthesis?
Friedberg, E. C., Lehmann, A. R., & Fuchs, R. P. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.032 · Cited by 376 · see citing works
Self-citationDirect binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1–Npl4
Meyer, H. H., Wang, Y., & Warren, G. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf579 · Cited by 363 · see citing works
Seigneurin-Berny, D., Verdel, A., Curtet, S., Lemercier, C., Garin, J., Rousseaux, S., & Khochbin, S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.23.8035-8044.2001 · Cited by 335 · 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-citationKannouche, P. L., de Henestrosa, A. R. F., Coull, B. J., Vidal, A. E., Gray, C., Zicha, D., Woodgate, R., & Lehmann, A. R. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf618 · Cited by 190 · see citing works
Self-citationBurnouf, D., Oliéric, V., Wagner, J. E., 藤井, 慎., Reinbolt, J., Fuchs, R. P., & Dumas, P. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.11.049 · Cited by 111 · see citing works
Kannouche, P. L., de Henestrosa, A. R. F., Coull, B. J., Vidal, A. E., Gray, C., Zicha, D., Woodgate, R., & Lehmann, A. R. (2003) · The EMBO Journal · doi:10.1093/emboj/7595006 · Cited by 96 · see citing works
Self-citationVidal, A. E., Kannouche, P. L., Podust, V. N., Yang, W., Lehmann, A. R., & Woodgate, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406511200 · Cited by 90 · see citing works
Self-citationLehmann, A. R. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00518-9 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368 · see citing works
Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679 · see citing works
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
The DNA Damage Response: Ten Years After
Harper, J. W., & Elledge, S. J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.015 · Cited by 1,705 · see citing works
The increasing complexity of the ubiquitin code
Yau, R., & Rape, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3358 · Cited by 1,054 · see citing works
Post-translational modifications in signal integration
Deribe, Y. L., Pawson, T., & Dikic, I. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1842 · Cited by 876 · see citing works
Self-citationY-family DNA polymerases and their role in tolerance of cellular DNA damage
Sale, J. E., Lehmann, A. R., & Woodgate, R. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3289 · Cited by 665 · see citing works
Self-citationEukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance
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
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
Self-citationTranslesion synthesis: Y-family polymerases and the polymerase switch
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
Self-citationForging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork
Choe, K. N., & Moldovan, G.-L. (2017) · Molecular Cell · doi:10.1016/j.molcel.2016.12.020 · Cited by 325 · see citing works
Goodman, M. F., & Woodgate, R. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a010363 · Cited by 317 · see citing works
Translesion DNA Synthesis and Mutagenesis in Eukaryotes
Sale, J. E. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012708 · Cited by 282 · see citing works
Karras, G. I., & Jentsch, S. (2010) · Cell · doi:10.1016/j.cell.2010.02.028 · Cited by 282 · see citing works
Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals
Shachar, S., Ziv, O., Avkin, S., Adar, S., Wittschieben, J., Reißner, T., Chaney, S., Friedberg, E. C., Wang, Z., Carell, T., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2008.281 · Cited by 284 · see citing works
Edmunds, C. E., Simpson, L. J., & Sale, J. E. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.024 · Cited by 239 · see citing works
Vujanovic, M., Krietsch, J., Raso, M. C., Terraneo, N., Zellweger, R., Schmid, J. A., Taglialatela, A., Huang, J.-W., Holland, C. L., Zwicky, K., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.010 · Cited by 227 · see citing works
PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells
Hendel, A., Krijger, P. H. L., Diamant, N., Goren, Z., Langerak, P., Kim, J., Reißner, T., Lee, K.-Y., Geacintov, N. E., Carell, T., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002262 · Cited by 132 · see citing works
USP7 Is a Master Regulator of Genome Stability
Valles, G. J., Bezsonova, I., Woodgate, R., & Ashton, N. W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00717 · Cited by 114 · see citing works
“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).”
BackgroundChang, D. J., Lupardus, P. J., & Cimprich, K. A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606799200 · Cited by 101 · see citing works
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
DNA polymerases and human diseases
Sweasy, J. B., Lauper, J. M., & Eckert, K. A. (2006) · Radiation Research · doi:10.1667/rr0706.1 · Cited by 93 · see citing works
USP7 is essential for maintaining Rad18 stability and DNA damage tolerance.
Zlatanou, A., Sabbioneda, S., Miller, E. S., Greenwalt, A., Aggathanggelou, A., Maurice, M. M., Lehmann, A. R., Stankovic, T., Reverdy, C., Colland, F., et al. (2016) · Oncogene · doi:10.1038/onc.2015.149 · Cited by 77 · see citing works
Self-citationUSP7 is a suppressor of PCNA ubiquitination and oxidative-stress-induced mutagenesis in human cells.
Kashiwaba, S.-I., Kanao, R., Masuda, Y., Kusumoto-Matsuo, R., Hanaoka, F., & Masutani, C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.11.014 · Cited by 71 · see citing works
Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability
Galanos, P., Pappas, G., Polyzos, A., Kotsinas, A., Svolaki, I., Giakoumakis, N. N., Glytsou, C., Pateras, I. S., Swain, U., Souliotis, V. L., et al. (2018) · Genome Biology · doi:10.1186/s13059-018-1401-9 · Cited by 67 · see citing works
Targeting the Translesion Synthesis Pathway for the Development of Anti-Cancer Chemotherapeutics
Korzhnev, D. M., & Hadden, M. K. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00596 · Cited by 58 · see citing works
Jung, Y.-S., Qian, Y., & Chen, X. (2012) · DNA Repair · doi:10.1016/j.dnarep.2011.10.017 · Cited by 57 · see citing works
USP1-Trapping Lesions as a Source of DNA Replication Stress and Genomic Instability
Coleman, K. E., Yin, Y., Lui, S. K. L., Keegan, S., Fenyo, D., Smith, D. J., Rothenberg, E., & Huang, T. T. (2022) · Nature Communications · doi:10.1038/s41467-022-29369-3 · Cited by 50 · see citing works
Sertic, S., Mollica, A., Campus, I., Roma, S., Tumini, E., Aguilera, A., & Muzi-Falconi, M. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.02.017 · Cited by 45 · see citing works
Mansilla, S. F., Bertolin, A. P., Bergoglio, V., Pillaire, M.-J., González Besteiro, M. A., Luzzani, C., Miriuka, S. G., Cazaux, C., Hoffmann, J.-S., & Gottifredi, V. (2016) · eLife · doi:10.7554/elife.18020 · Cited by 43 · see citing works
Temviriyanukul, P., van Hees-Stuivenberg, S., Delbos, F., Jacobs, H., de Wind, N., & Jansen, J. G. (2012) · DNA Repair · doi:10.1016/j.dnarep.2012.03.007 · Cited by 41 · see citing works
Cell cycle stage-specific roles of Rad18 in tolerance and repair of oxidative DNA damage
Yang, Y., Durando, M., Smith-Roe, S. L., Sproul, C., Greenwalt, A. M., Kaufmann, W., Oh, S., Hendrickson, E. A., & Vaziri, C. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks1325 · Cited by 33 · see citing works
Villafañez, F., García, I. A., Carbajosa, S., Pansa, M. F., Mansilla, S., Llorens, M. C., Angiolini, V., Guantay, L., Jacobs, H., Madauss, K. P., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0724-7 · Cited by 30 · see citing works
A new nuclease member of the FAN club
Huang, M., & D'Andrea, A. D. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb0810-926 · Cited by 29 · see citing works
Masuda, Y., Kanao, R., Kawai, H., Kukimoto, I., & Masutani, C. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005167 · Cited by 18 · see citing works
- Authors
- Bienko, M., Green, C. M., Crosetto, N., Rudolf, F., Zapart, G., Coull, B., Kannouche, P., Wider, G., Peter, M., Lehmann, A. R., Hofmann, K., & Dikic, I.
- Affiliations
- Institute for Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
- Goethe University Frankfurt (DE)
- Corresponding author
- Crosetto, Nicola
- Rudolf, Fabian
- Coull, Barry
- Kannouche, Patricia
- ORCID
- Venue
- Science
- Published
- 2005-12-16
- Volume
- 310
- Issue
- 5755
- Pages
- 1821-1824
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2169950973
- Cited by
- 712
- References
- 18
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 15 · 2023: 15 · 2022: 17 · 2021: 36 · 2020: 37 · 2019: 20 · 2018: 23 · 2017: 33 · 2016: 37 · 2015: 34 · 2014: 25 · 2013: 36 · 2012: 66
- FWCI
- 15.95
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- 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 › Genomics and Chromatin Dynamics
- Keywords
- translesion synthesis, Y-family DNA polymerases, ubiquitin-binding domain, PCNA ubiquitination, DNA damage bypass, xeroderma pigmentosum variant, replication factories, DNA repair
- MeSH terms
- DNA Polymerase iota, Y-Family DNA Polymerases, Amino Acid Sequence, Animals, Cell Line, DNA, DNA Damage, DNA-Directed DNA Polymerase, DNA Repair, DNA Replication, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Protein Binding, Protein Conformation, Recombinant Fusion Proteins, Transfection, Xeroderma Pigmentosum, Zinc Fingers, Point Mutation, Protein Structure, Tertiary, Proliferating Cell Nuclear Antigen, Computational Biology, Nuclear Magnetic Resonance, Biomolecular, Amino Acid Motifs, Ubiquitin, Protein Interaction Mapping, Hydrophobic and Hydrophilic Interactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
