Key Points
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Structure-specific endonucleases (SSEs) process various types of DNA secondary structures that arise during DNA replication, repair, recombination and transcription, and are important for the maintenance of genome stability.
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Elaborate regulatory mechanisms ensure that SSEs act in an efficient, specific and timely manner so that they do not themselves become a source of genome instability.
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The control of SSEs relies on a combination of catalytic regulation; modulation of their cellular localization, which regulates their targeting to the appropriate substrate or instead ensures their sequestration to reduce the risk of uncontrolled DNA processing; and protein turnover.
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SSEs can function genome-wide, such as during the repair of DNA adducts by nucleotide excision repair, or their function can be specific to genomic loci that are prone to the formation of DNA secondary structures that need to be processed during replication and/or transcription. Such loci include, for example, the ribosomal DNA or telomeres, which contain DNA repeats, or regions that replicate late in S phase and therefore might not be replicated on time before the onset of mitosis, such as common fragile sites.
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The control of SSEs is critical during DNA replication, during which inappropriate SSE activity, especially of MUS81 nucleases, can have dire consequences for genome stability.
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Nuclease scaffolds are particularly important for the regulation of SSEs, by helping in their efficient recruitment to DNA and coordination with other factors. Nuclease scaffolds can directly modulate the catalytic activity of SSEs and change their substrate specificity. Some scaffolds are dedicated to the control of a single SSE, whereas others control several SSEs, either independently or by coordinating their activity within the same pathway.
Abstract
Structure-specific endonucleases (SSEs) have key roles in DNA replication, recombination and repair, and emerging roles in transcription. These enzymes have specificity for DNA secondary structure rather than for sequence, and therefore their activity must be precisely controlled to ensure genome stability. In this Review, we discuss how SSEs are controlled as part of genome maintenance pathways in eukaryotes, with an emphasis on the elaborate mechanisms that regulate the members of the major SSE families — including the xeroderma pigmentosum group F-complementing protein (XPF) and MMS and UV-sensitive protein 81 (MUS81)-dependent nucleases, and the flap endonuclease 1 (FEN1), XPG and XPG-like endonuclease 1 (GEN1) enzymes — during processes such as DNA adduct repair, Holliday junction processing and replication stress. We also discuss newly characterized connections between SSEs and other classes of DNA-remodelling enzymes and cell cycle control machineries, which reveal the importance of SSE scaffolds such as the synthetic lethal of unknown function 4 (SLX4) tumour suppressor for the maintenance of genome stability.
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References
- 1
Lyamichev, V., Brow, M. A. & Dahlberg, J. E. Structure-specific endonucleolytic cleavage of nucleic acids by eubacterial DNA polymerases. Science 260, 778–783 (1993).
- 2
Robins, P., Pappin, D. J., Wood, R. D. & Lindahl, T. Structural and functional homology between mammalian DNase IV and the 5′-nuclease domain of Escherichia coli DNA polymerase I. J. Biol. Chem. 269, 28535–28538 (1994).
- 3
Harrington, J. J. & Lieber, M. R. The characterization of a mammalian DNA structure-specific endonuclease. EMBO J. 13, 1235–1246 (1994).
- 4
Harrington, J. J. & Lieber, M. R. Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair. Genes Dev. 8, 1344–1355 (1994).
- 5
O'Donovan, A., Davies, A. A., Moggs, J. G., West, S. C. & Wood, R. D. XPG endonuclease makes the 3′ incision in human DNA nucleotide excision repair. Nature 371, 432–435 (1994).
- 6
Davies, A. A., Friedberg, E. C., Tomkinson, A. E., Wood, R. D. & West, S. C. Role of the Rad1 and Rad10 proteins in nucleotide excision repair and recombination. J. Biol. Chem. 270, 24638–24641 (1995).
- 7
Sijbers, A. M. et al. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Nucleic Acids Res. 86, 811–822 (1996).
- 8
Brookman, K. W. et al. ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs. Mol. Cell. Biol. 16, 6553–6562 (1996).
- 9
Mizuuchi, K., Kemper, B., Hays, J. & Weisberg, R. A. T4 endonuclease VII cleaves holliday structures. Cell 29, 357–365 (1982).
- 10
Dunderdale, H. J. et al. Formation and resolution of recombination intermediates by E. coli RecA and RuvC proteins. Nature 354, 506–510 (1991).
- 11
Iwasaki, H., Takahagi, M., Shiba, T., Nakata, A. & Shinagawa, H. Escherichia coli RuvC protein is an endonuclease that resolves the Holliday structure. EMBO J. 10, 4381–4389 (1991).
- 12
Boddy, M. N. et al. Mus81–Eme1 are essential components of a Holliday junction resolvase. Cell 107, 537–548 (2001).
- 13
Chen, X. B. et al. Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol. Cell 8, 1117–1127 (2001).
- 14
Ip, S. C. Y. et al. Identification of Holliday junction resolvases from humans and yeast. Nature 456, 357–361 (2008).
- 15
Fekairi, S. et al. Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell 138, 78–89 (2009).
- 16
Munoz, I. M. et al. Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol. Cell 35, 116–127 (2009).
- 17
Svendsen, J. M. et al. Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell 138, 63–77 (2009).
- 18
Andersen, S. L. et al. Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination. Mol. Cell 35, 128–135 (2009). References 15–18 describe the identification of human SLX4 and how it binds multiple proteins and/or complexes that are involved in genome maintenance, which include XPF–ERCC1, SLX1 and MUS81–EME1.
- 19
Rass, U. et al. Mechanism of Holliday junction resolution by the human GEN1 protein. Genes Dev. 24, 1559–1569 (2010).
- 20
Manandhar, M., Boulware, K. S. & Wood, R. D. The ERCC1 and ERCC4 (XPF) genes and gene products. Gene 569, 153–161 (2015).
- 21
Tsutakawa, S. E., Lafrance-Vanasse, J. & Tainer, J. A. The cutting edges in DNA repair, licensing, and fidelity: DNA and RNA repair nucleases sculpt DNA to measure twice, cut once. DNA Repair (Amsterdam) 19, 95–107 (2014).
- 22
Finger, L. D. et al. The wonders of flap endonucleases: structure, function, mechanism and regulation. Subcell. Biochem. 62, 301–326 (2012).
- 23
Marteijn, J. A., Lans, H., Vermeulen, W. & Hoeijmakers, J. H. J. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 15, 465–481 (2014).
- 24
de Laat, W. L. et al. DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair. Genes Dev. 12, 2598–2609 (1998). Describes how RPA binds to single-stranded DNA with a defined polarity and contributes to the control of XPF–ERCC1 and XPG at sites of DNA damage.
- 25
Staresincic, L. et al. Coordination of dual incision and repair synthesis in human nucleotide excision repair. EMBO J. 28, 1111–1120 (2009). Describes how the first incision in NER is made by XPF–ERCC1, which is necessary for the second incision that is carried out by XPG.
- 26
Tripsianes, K. et al. Analysis of the XPA and ssDNA-binding surfaces on the central domain of human ERCC1 reveals evidence for subfunctionalization. Nucleic Acids Res. 35, 5789–5798 (2007).
- 27
Tsodikov, O. V. et al. Structural basis for the recruitment of ERCC1–XPF to nucleotide excision repair complexes by XPA. EMBO J. 26, 4768–4776 (2007).
- 28
Orelli, B. et al. The XPA-binding domain of ERCC1 is required for nucleotide excision repair but not other DNA repair pathways. J. Biol. Chem. 285, 3705–3712 (2010).
- 29
Sollier, J. et al. Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome stability. Mol. Cell 56, 1–9 (2014).
- 30
Fagbemi, A. F., Orelli, B. & Schärer, O. D. Regulation of endonuclease activity in human nucleotide excision repair. DNA Repair (Amsterdam) 10, 722–729 (2011).
- 31
Zhang, J. & Walter, J. C. Mechanism and regulation of incisions during DNA interstrand cross-link repair. DNA Repair (Amsterdam) 19, 1–8 (2014).
- 32
Lopez-Martinez, D., Liang, C.-C. & Cohn, M. A. Cellular response to DNA interstrand crosslinks: the Fanconi anemia pathway. Cell. Mol. Life Sci. 73, 1–18 (2016).
- 33
Hodskinson, M. R. G. et al. Mouse SLX4 is a tumor suppressor that stimulates the activity of the nuclease XPF–ERCC1 in DNA crosslink repair. Mol. Cell 54, 472–484 (2014). Demonstrates that SLX4 is a tumour suppressor in mice, together with detailed biochemical analyses of the stimulation of XPF–ERCC1 by SLX4 on ICL repair intermediates.
- 34
Douwel, D. K. et al. XPF–ERCC1 acts in unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4. Mol. Cell 54, 1–12 (2014). Describes the use of Xenopus laevis oocyte extracts to analyse the timely recruitment of FANCD2, SLX4 and XPF–ERCC1 to DNA during ICL repair.
- 35
Lachaud, C. et al. Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability. Science 351, 846–849 (2016). Shows that recruitment of FAN1 to ubiquitylated FANCD2 through its UBZ motif is crucial during replication inhibition, but is dispensable for ICL repair. A FAN1 variant from high-risk pancreatic cancer is not recruited to ubiquitylated FANCD2.
- 36
Wang, R. et al. DNA repair. Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1. Science 346, 1127–1130 (2014).
- 37
Liang, C.-C. et al. UHRF1 is a sensor for DNA interstrand crosslinks and recruits FANCD2 to initiate the Fanconi anemia pathway. Cell Rep. 10, 1947–1956 (2015).
- 38
Tian, Y. et al. UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold. Cell Rep. 10, 1957–1966 (2015). References 37 and 38 describe UHRF1 as a scaffold that is important in ICL repair and that recruits FANCD2, XPF–ERCC1 and MUS81–EME1.
- 39
Matos, J. & West, S. C. Holliday junction resolution: regulation in space and time. DNA Repair (Amsterdam) 19, 1–6 (2014).
- 40
Blanco, M. G. & Matos, J. Hold your horSSEs: controlling structure-selective endonucleases MUS81 and Yen1/GEN1. Front. Genet. 6, 253 (2015).
- 41
Matos, J., Blanco, M. G., Maslen, S., Skehel, J. M. & West, S. C. Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis. Cell 147, 158–172 (2011). Seminal study about cell cycle control of the Holliday junction resolvases Mus81–Mms4 and Yen1 in meiosis and mitosis in S. cerevisiae , and MUS81–EME1 and GEN1 in mitotic human cells.
- 42
Szakal, B. & Branzei, D. Premature Cdk1/Cdc5/Mus81 pathway activation induces aberrant replication and deleterious crossover. EMBO J. 32, 1155–1167 (2013). Describes the importance of the timely upregulation of Mus81–Mms4 in mitotic cells and the dire consequences if it is constitutively hyperactivate.
- 43
Gallo-Fernandez, M. et al. Cell cycle-dependent regulation of the nuclease activity of Mus81–Eme1/Mms4. Nucleic Acids Res. 40, 8325–8335 (2012).
- 44
Dehé, P.-M. et al. Regulation of Mus81–Eme1 Holliday junction resolvase in response to DNA damage. Nat. Struct. Mol. Biol. 20, 598–603 (2013).
- 45
Wehrkamp-Richter, S., Hyppa, R. W., Prudden, J., Smith, G. R. & Boddy, M. N. Meiotic DNA joint molecule resolution depends on Nse5–Nse6 of the Smc5–Smc6 holocomplex. Nucleic Acids Res. 40, 9633–9646 (2012).
- 46
Copsey, A. et al. Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions. PLoS Genet. 9, e1004071 (2013).
- 47
Sebesta, M. et al. Esc2 promotes Mus81 complex-activity via its SUMO-like and DNA binding domains. Nucleic Acids Res. http://dx.doi.org/10.1093/nar/gkw882 (2016).
- 48
Wyatt, H. D. M., Sarbajna, S., Matos, J. & West, S. C. Coordinated actions of SLX1–SLX4 and MUS81–EME1 for Holliday junction resolution in human cells. Mol. Cell 52, 1–14 (2013).
- 49
Castor, D. et al. Cooperative control of Holliday junction resolution and DNA repair by the SLX1 and MUS81–EME1 nucleases. Mol. Cell 52, 1–13 (2013). References 48 and 49 show that SLX4 controls and coordinates Holliday junction resolution by both SLX1 and MUS81–EME1.
- 50
Eissler, C. L. et al. The Cdk/Cdc14 module controls activation of the Yen1 holliday junction resolvase to promote genome stability. Mol. Cell 54, 80–93 (2014).
- 51
Blanco, M. G., Matos, J. & West, S. C. Dual control of Yen1 nuclease activity and cellular localization by Cdk and Cdc14 prevents genome instability. Mol. Cell 54, 94–106 (2014).
- 52
García-Luis, J., Clemente-Blanco, A., Aragón, L. & Machin, F. Cdc14 targets the Holliday junction resolvase Yen1 to the nucleus in early anaphase. Cell Cycle 13, 1392–1399 (2014).
- 53
Chan, Y. W. & West, S. C. Spatial control of the GEN1 Holliday junction resolvase ensures genome stability. Nat. Commun. 5, 4844–4811 (2014).
- 54
Bailly, A. P. et al. The Caenorhabditis elegans homolog of Gen1/Yen1 resolvases links DNA damage signaling to DNA double-strand break repair. PLoS Genet. 6, e1001025 (2010).
- 55
Bellendir, S. P. & Sekelsky, J. An elegans solution for crossover formation. PLoS Genet. 9, e1003658 (2013).
- 56
Andersen, S. L., Kuo, H. K., Savukoski, D., Brodsky, M. H. & Sekelsky, J. Three structure-selective endonucleases are essential in the absence of BLM helicase in Drosophila. PLoS Genet. 7, e1002315 (2011).
- 57
Ölmezer, G. et al. Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1. Nat. Commun. 7, 13157 (2016).
- 58
Kowalczykowski, S. C. An overview of the molecular mechanisms of recombinational DNA repair. Cold Spring Harb. Perspect. Biol. 7, a016410 (2015).
- 59
Mazón, G. & Symington, L. S. Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination intermediates. Mol. Cell 52, 63–74 (2013).
- 60
Balakrishnan, L. & Bambara, R. A. Flap endonuclease 1. Annu. Rev. Biochem. 82, 119–138 (2013).
- 61
Tsutakawa, S. E. et al. Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily. Cell 145, 198–211 (2011).
- 62
Tsutakawa, S. E. & Tainer, J. A. Double strand binding-single strand incision mechanism for human flap endonuclease: implications for the superfamily. Mech. Ageing Dev. 133, 195–202 (2012).
- 63
Zheng, L. et al. Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Nat. Med. 13, 812–819 (2007).
- 64
Li, X., Li, J., Harrington, J., Lieber, M. R. & Burgers, P. M. Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen. J. Biol. Chem. 270, 22109–22112 (1995).
- 65
Wu, X. et al. Processing of branched DNA intermediates by a complex of human FEN-1 and PCNA. Nucleic Acids Res. 24, 2036–2043 (1996).
- 66
Henneke, G., Koundrioukoff, S. & Hubscher, U. Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation. Oncogene 22, 4301–4313 (2003).
- 67
Guo, Z. et al. Sequential posttranslational modifications program FEN1 degradation during cell-cycle progression. Mol. Cell 47, 444–456 (2012). Identifies a mechanism that controls the programmed degradation of FEN1 through sequential phosphorylation, sumoylation and ubiquitylation of FEN1.
- 68
Guo, Z. et al. Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nat. Chem. Biol. 6, 766–773 (2010).
- 69
Hasan, S. et al. Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300. Mol. Cell 7, 1221–1231 (2001).
- 70
Choudhary, C. et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834–840 (2009).
- 71
Balakrishnan, L., Stewart, J., Polaczek, P., Campbell, J. L. & Bambara, R. A. Acetylation of Dna2 endonuclease/helicase and flap endonuclease 1 by p300 promotes DNA stability by creating long flap intermediates. J. Biol. Chem. 285, 4398–4404 (2010).
- 72
Bae, S. H., Bae, K. H., Kim, J. A. & Seo, Y. S. RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes. Nature 412, 456–461 (2001).
- 73
Friedrich-Heineken, E. et al. The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity. J. Mol. Biol. 353, 980–989 (2005).
- 74
Sharma, S. et al. Stimulation of flap endonuclease-1 by the Bloom's syndrome protein. J. Biol. Chem. 279, 9847–9856 (2004).
- 75
Wang, W. & Bambara, R. A. Human Bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure. J. Biol. Chem. 280, 5391–5399 (2005).
- 76
Brosh, R. M. et al. Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity. EMBO J. 20, 5791–5801 (2001).
- 77
Zheng, L. et al. Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks. EMBO Rep. 6, 83–89 (2005).
- 78
Sharma, S. et al. The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic Acids Res. 33, 6769–6781 (2005).
- 79
Sami, F. et al. RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin. Biochem. J. 468, 227–244 (2015).
- 80
Schurman, S. H. et al. Direct and indirect roles of RECQL4 in modulating base excision repair capacity. Hum. Mol. Genet. 18, 3470–3483 (2009).
- 81
Speina, E. et al. Human RECQL5beta stimulates flap endonuclease 1. Nucleic Acids Res. 38, 2904–2916 (2010).
- 82
Magdalou, I., Lopez, B. S., Pasero, P. & Lambert, S. A. E. The causes of replication stress and their consequences on genome stability and cell fate. Semin. Cell Dev. Biol. 30, 154–164 (2014).
- 83
García-Muse, T. & Aguilera, A. Transcription–replication conflicts: how they occur and how they are resolved. Nat. Rev. Mol. Cell Biol. 17, 553–563 (2016).
- 84
Berti, M. & Vindigni, A. Replication stress: getting back on track. Nat. Struct. Mol. Biol. 23, 103–109 (2016).
- 85
Guo, Z. et al. Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair. Mol. Cell. Biol. 28, 4310–4319 (2008).
- 86
Saharia, A. et al. FEN1 ensures telomere stability by facilitating replication fork re-initiation. J. Biol. Chem. 285, 27057–27066 (2010).
- 87
Teasley, D. C. et al. Flap endonuclease 1 limits telomere fragility on the leading strand. J. Biol. Chem. 290, 15133–15145 (2015).
- 88
Sharma, S. et al. WRN helicase and FEN-1 form a complex upon replication arrest and together process branchmigrating DNA structures associated with the replication fork. Mol. Biol. Cell 15, 734–750 (2004).
- 89
Cheng, I-C. et al. Wuho is a new member in maintaining genome stability through its interaction with flap endonuclease 1. PLoS Biol. 14, e1002349 (2016). Identification of WUHO as a positive and negative regulator of the flap and gap endonuclease functions of FEN1, respectively.
- 90
Chung, L. et al. The FEN1 E359K germline mutation disrupts the FEN1–WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. Oncogene 34, 902–911 (2015).
- 91
Shin, Y.-K., Amangyeld, T., Nguyen, T. A., Munashingha, P. R. & Seo, Y.-S. Human MUS81 complexes stimulate flap endonuclease 1. FEBS J. 279, 2412–2430 (2012).
- 92
Thu, H. P. T. et al. A physiological significance of the functional interaction between Mus81 and Rad27 in homologous recombination repair. Nucleic Acids Res. 43, 1684–1699 (2015).
- 93
Kang, M.-J. et al. Genetic and functional interactions between Mus81–Mms4 and Rad27. Nucleic Acids Res. 38, 7611–7625 (2010).
- 94
Chaudhury, I., Stroik, D. R. & Sobeck, A. FANCD2-controlled chromatin access of the Fanconi-associated nuclease FAN1 is crucial for the recovery of stalled replication forks. Mol. Cell. Biol. 34, 3939–3954 (2014).
- 95
Ciccia, A. et al. Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Mol. Cell 47, 396–409 (2012).
- 96
Yuan, J., Ghosal, G. & Chen, J. The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress. Mol. Cell 47, 410–421 (2012).
- 97
Weston, R. et al. ZRANB3 is a structure-specific ATP-dependent endonuclease involved in replication stress response. Genes Dev. 26, 1558–1572 (2012). References 95–97 describe how the translocase ZRANB3 is an ATP-dependent SSE that is recruited to ubiquitylated PCNA.
- 98
Badu-Nkansah, A., Mason, A. C., Eichman, B. F. & Cortez, D. Identification of a substrate recognition domain in the replication stress response protein zinc finger Ran-binding domain containing protein 3 (ZRANB3). J. Biol. Chem. 291 8251–8257 (2016).
- 99
Yusufzai, T. & Kadonaga, J. T. Annealing helicase 2 (AH2), a DNA-rewinding motor with an HNH motif. Proc. Natl Acad. Sci. USA 107, 20970–20973 (2010).
- 100
Sirbu, B. M. et al. Identification of proteins at active, stalled, and collapsed replication forks using isolation of proteins on nascent DNA (iPOND) coupled with mass spectrometry. J. Biol. Chem. 288, 31458–31467 (2013).
- 101
Zeman, M. K. & Cimprich, K. A. Finally, polyubiquitinated PCNA gets recognized. Mol. Cell 47, 333–334 (2012).
- 102
Yao, Q. et al. Structure and specificity of the bacterial cysteine methyltransferase effector NleE suggests a novel substrate in human DNA repair pathway. PLoS Pathog. 10, e1004522 (2014).
- 103
Doe, C. L., Ahn, J. S., Dixon, J. & Whitby, M. C. Mus81–Eme1 and Rqh1 involvement in processing stalled and collapsed replication forks. J. Biol. Chem. 277, 32753–32759 (2002).
- 104
Boddy, M. N. et al. Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Mol. Cell. Biol. 20, 8758–8766 (2000).
- 105
Interthal, H. & Heyer, W. D. MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae. Mol. Gen. Genet. 263, 812–827 (2000).
- 106
Osman, F. & Whitby, M. Exploring the roles of Mus81–Eme1/Mms4 at perturbed replication forks. DNA Repair 6, 1004–1017 (2007).
- 107
Abraham, J. et al. Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. EMBO J. 22, 6137–6147 (2003).
- 108
Dendouga, N. et al. Disruption of murine Mus81 increases genomic instability and DNA damage sensitivity but does not promote tumorigenesis. Mol. Cell. Biol. 25, 7569–7579 (2005).
- 109
Hanada, K. et al. The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks. Nat. Struct. Mol. Biol. 14, 1096–1104 (2007).
- 110
Regairaz, M. et al. Mus81-mediated DNA cleavage resolves replication forks stalled by topoisomerase I–DNA complexes. J. Cell Biol. 195, 739–749 (2011).
- 111
Franchitto, A. et al. Replication fork stalling in WRN-deficient cells is overcome by prompt activation of a MUS81-dependent pathway. J. Cell Biol. 183, 241–252 (2008).
- 112
Noguchi, E., Noguchi, C., Du, L.-L. & Russell, P. Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1. Mol. Cell. Biol. 23, 7861–7874 (2003).
- 113
Noguchi, E., Noguchi, C., McDonald, W. H., Yates, J. R. & Russell, P. Swi1 and Swi3 are components of a replication fork protection complex in fission yeast. Mol. Cell. Biol. 24, 8342–8355 (2004).
- 114
Bellaoui, M. et al. Elg1 forms an alternative RFC complex important for DNA replication and genome integrity. EMBO J. 22, 4304–4313 (2003).
- 115
Pebernard, S., McDonald, W. H., Pavlova, Y., Yates, J. R. & Boddy, M. N. Nse1, Nse2, and a novel subunit of the Smc5–Smc6 complex, Nse3, play a crucial role in meiosis. Mol. Biol. Cell 15, 4866–4876 (2004).
- 116
Boddy, M. N. et al. Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60. Mol. Cell. Biol. 23, 5939–5946 (2003).
- 117
Irmisch, A., Ampatzidou, E., Mizuno, K., O'Connell, M. J. & Murray, J. M. Smc5/6 maintains stalled replication forks in a recombination-competent conformation. EMBO J. 28, 144–155 (2009).
- 118
Torres-Rosell, J. et al. SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat. Cell Biol. 7, 412–419 (2005).
- 119
Mayle, R. et al. Mus81 and converging forks limit the mutagenicity of replication fork breakage. Science 349, 742–747 (2015).
- 120
Gao, H., Chen, X.-B. & McGowan, C. H. Mus81 endonuclease localizes to nucleoli and to regions of DNA damage in human S-phase cells. Mol. Biol. Cell 14, 4826–4834 (2003).
- 121
Shimura, T. et al. Bloom's syndrome helicase and Mus81 are required to induce transient double-strand DNA breaks in response to DNA replication stress. J. Mol. Biol. 375, 1152–1164 (2008).
- 122
Pepe, A. & West, S. C. MUS81–EME2 promotes replication fork restart. Cell Rep. 7, 1048–1055 (2014).
- 123
Fu, H. et al. The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage. Nat. Commun. 6, 6746–6714 (2015).
- 124
Xing, M. et al. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response. Oncotarget 6, 37638–37646 (2015).
- 125
Zhang, R. et al. BLM helicase facilitates Mus81 endonuclease activity in human cells. Cancer Res. 65, 2526–2531 (2005).
- 126
Fadden, A. J. et al. A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes. Nucleic Acids Res. 41, 9741–9752 (2013).
- 127
Kikuchi, K. et al. Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination. Cancer Res. 73, 4362–4371 (2013).
- 128
Kai, M., Boddy, M. N., Russell, P. & Wang, T. S.-F. Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress. Genes Dev. 19, 919–932 (2005). Provides evidence of the potentially deleterious effects of Mus81 during replication, especially when not controlled by Cds1.
- 129
Froget, B., Blaisonneau, J., Lambert, S. & Baldacci, G. Cleavage of stalled forks by fission yeast Mus81/Eme1 in absence of DNA replication checkpoint. Mol. Biol. Cell 19, 445–456 (2008).
- 130
Saugar, I. et al. Temporal regulation of the Mus81–Mms4 endonuclease ensures cell survival under conditions of DNA damage. Nucleic Acids Res. 41, 8943–8958 (2013).
- 131
Schwartz, E. K. et al. Mus81–Mms4 function as a single heterodimer to cleave nicked intermediates in recombinational DNA repair. Mol. Cell. Biol. 32, 3065–3080 (2012).
- 132
Gaillard, P.-H. L., Noguchi, E., Shanahan, P. & Russell, P. The endogenous Mus81–Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Mol. Cell 12, 747–759 (2003).
- 133
Domínguez-Kelly, R. et al. Wee1 controls genomic stability during replication by regulating the Mus81–Eme1 endonuclease. J. Cell Biol. 194, 567–579 (2011).
- 134
Beck, H. et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol. Cell. Biol. 32, 4226–4236 (2012).
- 135
Forment, J. V., Blasius, M., Guerini, I. & Jackson, S. P. Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by Chk1 inactivation. PLoS ONE 6, e23517 (2011).
- 136
Murfuni, I. et al. Survival of the replication checkpoint deficient cells requires MUS81–RAD52 function. PLoS Genet. 9, e1003910 (2013).
- 137
Técher, H. et al. Signaling from Mus81–Eme2-dependent DNA damage elicited by Chk1 deficiency modulates replication fork speed and origin usage. Cell Rep. 14, 1114–1127 (2016).
- 138
Duda, H. et al. A mechanism for controlled breakage of under-replicated chromosomes during mitosis. Dev. Cell 1, 740–755 (2016).
- 139
Ohouo, P. Y., Bastos de Oliveira, F. M., Almeida, B. S. & Smolka, M. B. DNA damage signaling recruits the Rtt107–Slx4 scaffolds via Dpb11 to mediate replication stress response. Mol. Cell 39, 300–306 (2010).
- 140
Ohouo, P. Y., Bastos de Oliveira, F. M., Liu, Y., Ma, C. J. & Smolka, M. B. DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9. Nature 493, 120–124 (2013).
- 141
Princz, L. N., Gritenaite, D. & Pfander, B. The Slx4–Dpb11 scaffold complex: coordinating the response to replication fork stalling in S-phase and the subsequent mitosis. Cell Cycle 14, 488–494 (2015).
- 142
Balint, A. et al. Assembly of Slx4 signaling complexes behind DNA replication forks. EMBO J. 34, 2182–2197 (2015).
- 143
Gritenaite, D. et al. A cell cycle-regulated Slx4–Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication. Genes Dev. 28, 1604–1619 (2014).
- 144
Cussiol, J. R., Jablonowski, C. M., Yimit, A., Brown, G. W. & Smolka, M. B. Dampening DNA damage checkpoint signalling via coordinated BRCT domain interactions. EMBO J. 34, 1704–1717 (2015).
- 145
Princz, L. N. et al. Dbf4-dependent kinase (DDK) and the Rtt107 scaffold promote Mus81–Mms4 resolvase activation during mitosis. EMBO J. http://dx.doi.org/10.15252/embj.201694831 (2017).
- 146
Neelsen, K. J. & Lopes, M. Replication fork reversal in eukaryotes: from dead end to dynamic response. Nat. Rev. Mol. Cell Biol. 16, 207–220 (2015).
- 147
Neelsen, K. J., Zanini, I. M. Y., Herrador, R. & Lopes, M. Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates. J. Cell Biol. 200, 699–708 (2013).
- 148
Sogo, J. M., Lopes, M. & Foiani, M. Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects. Science 297, 599–602 (2002).
- 149
Branzei, D. & Foiani, M. Maintaining genome stability at the replication fork. Nat. Rev. Mol. Cell Biol. 11, 208–219 (2010).
- 150
Ragland, R. L. et al. RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells. Genes Dev. 27, 2259–2273 (2013).
- 151
Saito, T. T., Youds, J. L., Boulton, S. J. & Colaiácovo, M. P. Caenorhabditis elegans HIM-18/SLX-4 interacts with SLX-1 and XPF-1 and maintains genomic integrity in the germline by processing recombination intermediates. PLoS Genet. 5, e1000735 (2009).
- 152
Fricke, W. M. & Brill, S. J. Slx1–Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1–Top3. Genes Dev. 17, 1768–1778 (2003).
- 153
Coulon, S. et al. Slx1–Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast. Mol. Biol. Cell 15, 71–80 (2004).
- 154
Zakharyevich, K., Tang, S., Ma, Y. & Hunter, N. Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase. Cell 149, 334–347 (2012).
- 155
Guervilly, J.-H. et al. The SLX4 complex is a SUMO E3 ligase that impacts on replication stress outcome and genome stability. Mol. Cell 57, 123–137 (2015).
- 156
Ouyang, J. et al. Noncovalent interactions with SUMO and ubiquitin orchestrate distinct functions of the SLX4 complex in genome maintenance. Mol. Cell 57, 108–122 (2015).
- 157
Minocherhomji, S. et al. Replication stress activates DNA repair synthesis in mitosis. Nature 528, 1–17 (2015).
- 158
Ying, S. et al. MUS81 promotes common fragile site expression. Nat. Cell Biol. 15, 1001–1007 (2013).
- 159
Naim, V., Wilhelm, T., Debatisse, M. & Rosselli, F. ERCC1 and MUS81–EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis. Nat. Cell Biol. 15, 1008–1015 (2013).
- 160
Bergoglio, V. et al. DNA synthesis by Pol η promotes fragile site stability by preventing under-replicated DNA in mitosis. J. Cell Biol. 201, 395–408 (2013).
- 161
Zhu, X.-D. et al. ERCC1/XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol. Cell 12, 1489–1498 (2003).
- 162
Zeng, S. et al. Telomere recombination requires the MUS81 endonuclease. Nat. Cell Biol. 11, 616–623 (2009).
- 163
Vannier, J.-B., Depeiges, A., White, C. & Gallego, M. E. ERCC1/XPF protects short telomeres from homologous recombination in Arabidopsis thaliana. PLoS Genet. 5, e1000380 (2009).
- 164
Wan, B. et al. SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres. Cell Rep. 4, 861–869 (2013).
- 165
Wilson, J. S. J. et al. Localization-dependent and -independent roles of SLX4 in regulating telomeres. Cell Rep. 4, 853–860 (2013).
- 166
Sarkar, J. et al. SLX4 contributes to telomere preservation and regulated processing of telomeric joint molecule intermediates. Nucleic Acids Res. 43, 5912–5923 (2015).
- 167
Vannier, J.-B., Pavicic-Kaltenbrunner, V., Petalcorin, M. I. R., Ding, H. & Boulton, S. J. RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell 149, 795–806 (2012).
- 168
Saint-Léger, A. et al. The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres. Cell Cycle 13, 2469–2474 (2014).
- 169
Poulet, A. et al. TRF2 promotes, remodels and protects telomeric Holliday junctions. EMBO J. 28, 641–651 (2009).
- 170
Kim, Y. Nuclease delivery: versatile functions of SLX4/FANCP in genome maintenance. Mol. Cells 37, 569–574 (2014).
- 171
Lachaud, C. et al. Distinct functional roles for the two SLX4 ubiquitin-binding UBZ domains mutated in Fanconi anemia. J. Cell Sci. 127, 2811–2817 (2014).
- 172
Sarangi, P. et al. Sumoylation of the Rad1 nuclease promotes DNA repair and regulates its DNA association. Nucleic Acids Res. 42, 6393–6404 (2014).
- 173
Flott, S. et al. Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast. Mol. Cell. Biol. 27, 6433–6445 (2007).
- 174
Sarangi, P. et al. A versatile scaffold contributes to damage survival via sumoylation and nuclease interactions. Cell Rep. 9, 143–152 (2014).
- 175
Li, F. et al. Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Mol. Cell 30, 325–335 (2008).
- 176
Zhang, J.-M. et al. Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2. PLoS Biol. 12, e1001946 (2014). Identifies Pxd1 as a novel nuclease scaffold in fission yeast that differentially regulates Rad16–Swi10 and Dna2 endonucleases.
- 177
Bétous, R. et al. SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication. Genes Dev. 26, 151–162 (2012).
- 178
Fugger, K. et al. FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress. Nat. Commun. 4, 1423 (2013).
- 179
Burman, B., Zhang, Z. Z., Pegoraro, G., Lieb, J. D. & Misteli, T. Histone modifications predispose genome regions to breakage and translocation. Genes Dev. 29, 1393–1402 (2015).
- 180
Le May, N. et al. NER factors are recruited to active promoters and facilitate chromatin modification for transcription in the absence of exogenous genotoxic attack. Mol. Cell 38, 54–66 (2010).
- 181
Trego, K. S. et al. Non-catalytic roles for XPG with BRCA1 and BRCA2 in homologous recombination and genome stability. Mol. Cell 61, 535–546 (2016).
- 182
Laguette, N. et al. Premature activation of the SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing. Cell 156, 134–145 (2014).
- 183
Hartung, M. L. et al. H. pylori-induced DNA strand breaks are introduced by nucleotide excision repair endonucleases and promote NF-κB target gene expression. Cell Rep. 13, 70–79 (2015).
- 184
Ho, S. S. W. et al. The DNA structure-specific endonuclease MUS81 mediates DNA sensor STING-dependent host rejection of prostate cancer cells. Immunity 44, 1177–1189 (2016).
- 185
Nishino, T., Komori, K., Ishino, Y. & Morikawa, K. X-ray and biochemical anatomy of an archaeal XPF/Rad1/Mus81 family nuclease: similarity between its endonuclease domain and restriction enzymes. Structure 11, 445–457 (2003).
- 186
Ciccia, A., McDonald, N. & West, S. C. Structural and functional relationships of the XPF/MUS81 family of proteins. Annu. Rev. Biochem. 77, 259–287 (2008).
- 187
Sgouros, J., Gaillard, P. H. & Wood, R. D. A relationship betweena DNA-repair/recombination nuclease family and archaeal helicases. Trends Biochem. Sci. 24, 95–97 (1999).
- 188
Roberts, J. A., Bell, S. D. & White, M. F. An archaeal XPF repair endonuclease dependent on a heterotrimeric PCNA. Mol. Microbiol. 48, 361–371 (2003).
- 189
Gaillard, P. H. & Wood, R. D. Activity of individual ERCC1 and XPF subunits in DNA nucleotide excision repair. Nucleic Acids Res. 29, 872–879 (2001).
- 190
Xue, X., Sung, P. & Zhao, X. Functions and regulation of the multitasking FANCM family of DNA motor proteins. Genes Dev. 29, 1777–1788 (2015).
- 191
Smith, G. R., Boddy, M. N., Shanahan, P. & Russell, P. Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion. Genetics 165, 2289–2293 (2003).
- 192
de los Santos, T., Loidl, J., Larkin, B. & Hollingsworth, N. M. A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae. Genetics 159, 1511–1525 (2001).
- 193
Sekelsky, J. J., McKim, K. S., Chin, G. M. & Hawley, R. S. The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics 141, 619–627 (1995).
- 194
O'neil, N. J. et al. Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1 during Caenorhabditis elegans meiosis. PLoS Genet. 9, e1003582 (2013).
- 195
Makharashvili, N. et al. Catalytic and noncatalytic roles of the CtIP endonuclease in double-strand break end resection. Mol. Cell 54, 1022–1033 (2014).
- 196
Wang, H. et al. CtIP maintains stability at common fragile sites and inverted repeats by end resection-independent endonuclease activity. Mol. Cell 54, 1012–1021 (2014).
- 197
Matos, J., Blanco, M. G. & West, S. C. Cell-cycle kinases coordinate the resolution of recombination intermediates with chromosome segregation. Cell Rep. 4, 76–86 (2013).
- 198
Couch, F. B. & Cortez, D. Fork reversal, too much of a good thing. Cell Cycle 13, 1049–1050 (2014).
- 199
Kim, Y. et al. Mutations of the SLX4 gene in Fanconi anemia. Nat. Genet. 43, 142–146 (2011).
- 200
Kaliraman, V. & Brill, S. J. Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae. Curr. Genet. 41, 389–400 (2002).
- 201
Li, F. et al. Role of Saw1 in Rad1/Rad10 complex assembly at recombination intermediates in budding yeast. EMBO J. 32, 461–472 (2013). Demonstrates that the scaffold protein Saw1 is a structure-specific DNA-binding protein that targets and activates Rad1–Rad10 during SSA.
Acknowledgements
The authors apologize for the many studies that were not cited owing to space limitations. The authors thank all members of their laboratory for stimulating discussions, especially S. Scaglione, J.-H. Guervilly and B. LLorente. The authors thank S. Scaglione and J.-H. Guervilly for their critical and careful reading of the manuscript. The authors also thank R. Wood, P. Russell, N. Boddy, P. McHugh and J. Matos for enlightening and enthusiastic discussions, with special thanks to R. Wood, P. Russell and N. Boddy for their feedback on the manuscript. Finally, the authors thank the referees for their thorough reviewing, which has undoubtedly helped improve the manuscript. This work was supported by grants from the Institut National du Cancer (PLBIO 2012–111), Agence Nationale de la Recherche (ANR Blanc EME1PHOSUMO) and the Siric-Cancéropôle PACA (AAP Projets émergents 2015).
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Supplementary information
Supplementary information S1
Conserved families of structure-specific endonucleases (PDF 519 kb)
Supplementary information S2
Positive and negative regulation of SSEs (PDF 207 kb)
Supplementary information S3
Controlling the resolution of joint molecules by SSEs in meiosis. (PDF 783 kb)
Supplementary information S4
Structure-specific endonuclease scaffolds. (PDF 238 kb)
Glossary
- Single-stranded flaps
-
Single-stranded DNA protrusions from duplex DNA with either 5′ phosphate or 3′ hydroxyl ends.
- Stem–loops
-
DNA structures that comprise two adjacent complementary sequences that form duplex DNA (the stem) with an intervening single-stranded closed loop.
- Displacement loops
-
(D-loops). DNA structures that form early during homologous recombination by the invasion of duplex DNA by complementary single-stranded DNA.
- Holliday junctions
-
Four-way DNA junction structures that form after complementary strand exchange between homologous sequences during DNA double-strand break repair by homologous recombination or during replication. Holliday junctions constitute covalent links between chromosomes.
- DNA adducts
-
Chemical compounds or proteins that are covalently linked to DNA.
- R-loops
-
Three-stranded nucleic acid structures that contain an RNA–DNA hybrid that results from the pairing of a nascent RNA with the DNA template during transcription.
- Fanconi anaemia core complex
-
A multiprotein complex that resolves blocks to DNA replication such as DNA interstrand crosslinks. Mutations in the complex cause Fanconi anaemia, which is characterized mainly by haematological problems and cancer predisposition.
- Trans-lesion DNA synthesis
-
Low-fidelity (and thereby mutagenic) DNA replication over damaged bases by specialized trans-lesion polymerases.
- Ubiquitin-binding motif
-
A modular protein domain that mediates the non-covalent binding to monoubiquitin and/or polyubiquitin chains.
- Double Holliday junctions
-
Structures that comprise two proximal Holliday junctions, which represent an intermediate stage of homologous recombination.
- Holliday junction dissolution
-
A process by which double Holliday junctions are merged into a hemicatenane structure, in which one of the strands of one duplex passes between the strands of the other duplex. This structure is processed by a single-strand cut that releases the two duplexes from one another.
- Bloom syndrome
-
A hereditary disorder that arises from mutations in the gene encoding the RecQ DNA helicase Bloom syndrome protein (BLM). It is characterized by growth deficiencies, sun sensitivity, immunodeficiency and predisposition to cancer.
- Okazaki fragments
-
DNA fragments that are synthesized during replication of the lagging strand by DNA polymerase-α (Polα) and Polδ; the fragments are joined together by DNA ligase I to form the continuous lagging strand.
- Common fragile sites
-
(CFSs). Chromosomal regions that are prone to replication stress. CFSs are a potential source of genome instability and are associated with chromosomal rearrangements in cancer.
- NPL4 zinc finger domain
-
(NZF domain). A domain that mediates binding to monoubiquitin and polyubiquitin.
- Winged-helix domain
-
A subclass of the helix-turn-helix DNA-binding domain that is found in DNA-processing enzymes and many transcription factors.
- S phase checkpoint
-
A signalling pathway that is triggered by replication stress and that delays cell cycle progression and protects the integrity of replication forks.
- Forkhead-associated domain
-
(FHA domain). A domain that mediates recognition of phosphopeptides.
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Dehé, PM., Gaillard, PH. Control of structure-specific endonucleases to maintain genome stability. Nat Rev Mol Cell Biol 18, 315–330 (2017). https://doi.org/10.1038/nrm.2016.177
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