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Nuclease Delivery: Versatile Functions of SLX4/FANCP in Genome Maintenance

  • Kim, Yonghwan (Department of Life Systems, Sookmyung Women's University)
  • Received : 2014.05.07
  • Accepted : 2014.05.28
  • Published : 2014.08.31

Abstract

As a scaffold, SLX4/FANCP interacts with multiple proteins involved in genome integrity. Although not having recognizable catalytic domains, SLX4 participates in diverse genome maintenance pathways by delivering nucleases where they are needed, and promoting their cooperative execution to prevent genomic instabilities. Physiological importance of SLX4 is emphasized by the identification of causative mutations of SLX4 genes in patients diagnosed with Fanconi anemia (FA), a rare recessive genetic disorder characterized by genomic instability and predisposition to cancers. Recent progress in understanding functional roles of SLX4 has greatly expanded our knowledge in the repair of DNA interstrand crosslinks (ICLs), Holliday junction (HJ) resolution, telomere homeostasis and regulation of DNA damage response induced by replication stress. Here, these diverse functions of SLX4 are reviewed in detail.

Keywords

References

  1. Ancelin, K., Brunori, M., Bauwens, S., Koering, C.E., Brun, C., Ricoul, M., Pommier, J.P., Sabatier, L., and Gilson, E. (2002). Targeting assay to study the cis functions of human telomeric proteins: evidence for inhibition of telomerase by TRF1 and for activation of telomere degradation by TRF2. Mol. Cell. Biol. 22, 3474-3487. https://doi.org/10.1128/MCB.22.10.3474-3487.2002
  2. Andersen, S.L., Bergstralh, D.T., Kohl, K.P., LaRocque, J.R., Moore, C.B., and Sekelsky, J. (2009). Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination. Mol. Cell 35, 128-135. https://doi.org/10.1016/j.molcel.2009.06.019
  3. Andersen, S.L., Kuo, H.K., Savukoski, D., Brodsky, M.H., and Sekelsky, J. (2011). Three structure-selective endonucleases are essential in the absence of BLM helicase in Drosophila. PLoS Genet. 7, e1002315. https://doi.org/10.1371/journal.pgen.1002315
  4. Bergstralh, D.T., and Sekelsky, J. (2008). Interstrand crosslink repair: can XPF-ERCC1 be let off the hook? Trends Genet. 24, 70-76. https://doi.org/10.1016/j.tig.2007.11.003
  5. Boddy, M.N., Gaillard, P.H., McDonald, W.H., Shanahan, P., Yates, J.R., 3rd, and Russell, P. (2001). Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107, 537-548. https://doi.org/10.1016/S0092-8674(01)00536-0
  6. Bogliolo, M., Schuster, B., Stoepker, C., Derkunt, B., Su, Y., Raams, A., Trujillo, J.P., Minguillon, J., Ramirez, M.J., Pujol, R., et al. (2013). Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause Fanconi anemia. Am. J. Hum. Genet. 92, 800-806. https://doi.org/10.1016/j.ajhg.2013.04.002
  7. Castor, D., Nair, N., Declais, A.C., Lachaud, C., Toth, R., Macartney, T.J., Lilley, D.M., Arthur, J.S., and Rouse, J. (2013). Cooperative control of holliday junction resolution and DNA repair by the SLX1 and MUS81-EME1 nucleases. Mol. Cell 52, 221-233. https://doi.org/10.1016/j.molcel.2013.08.036
  8. Cimprich, K.A., and Cortez, D. (2008). ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 9, 616-627. https://doi.org/10.1038/nrm2450
  9. Clerici, M., Paciotti, V., Baldo, V., Romano, M., Lucchini, G., and Longhese, M.P. (2001). Hyperactivation of the yeast DNA damage checkpoint by TEL1 and DDC2 overexpression. EMBO J. 20, 6485-6498. https://doi.org/10.1093/emboj/20.22.6485
  10. Coulon, S., Gaillard, P.H., Chahwan, C., McDonald, W.H., Yates, J.R., 3rd, and Russell, P. (2004). Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast. Mol. Biol. Cell 15, 71-80.
  11. D'Andrea, A.D. (2010). Susceptibility pathways in Fanconi's anemia and breast cancer. N. Engl. J. Med. 362, 1909-1919. https://doi.org/10.1056/NEJMra0809889
  12. De Silva, I.U., McHugh, P.J., Clingen, P.H., and Hartley, J.A. (2000). Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells. Mol. Cell. Biol. 20, 7980-7990. https://doi.org/10.1128/MCB.20.21.7980-7990.2000
  13. Deans, A.J., and West, S.C. (2011). DNA interstrand crosslink repair and cancer. Nat. Rev. Cancer 11, 467-480. https://doi.org/10.1038/nrc3088
  14. Dendouga, N., Gao, H., Moechars, D., Janicot, M., Vialard, J., and McGowan, C.H. (2005). Disruption of murine Mus81 increases genomic instability and DNA damage sensitivity but does not promote tumorigenesis. Mol. Cell. Biol. 25, 7569-7579. https://doi.org/10.1128/MCB.25.17.7569-7579.2005
  15. Fekairi, S., Scaglione, S., Chahwan, C., Taylor, E.R., Tissier, A., Coulon, S., Dong, M.Q., Ruse, C., Yates, J.R., 3rd, Russell, P., et al. (2009). Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell 138, 78-89. https://doi.org/10.1016/j.cell.2009.06.029
  16. Gaillard, P.H., Noguchi, E., Shanahan, P., and Russell, P. (2003). The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Mol. Cell 12, 747-759. https://doi.org/10.1016/S1097-2765(03)00342-3
  17. Garner, E., and Smogorzewska, A. (2011). Ubiquitylation and the Fanconi anemia pathway. FEBS Lett. 585, 2853-2860. https://doi.org/10.1016/j.febslet.2011.04.078
  18. Garner, E., Kim, Y., Lach, F.P., Kottemann, M.C., and Smogorzewska, A. (2013). Human GEN1 and the SLX4-associated nucleases MUS81 and SLX1 are essential for the resolution of replication-induced Holliday junctions. Cell Rep. 5, 207-215. https://doi.org/10.1016/j.celrep.2013.08.041
  19. Hanada, K., Budzowska, M., Modesti, M., Maas, A., Wyman, C., Essers, J., and Kanaar, R. (2006). The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. EMBO J. 25, 4921-4932. https://doi.org/10.1038/sj.emboj.7601344
  20. Hollingsworth, N.M., and Brill, S.J. (2004). The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions. Genes Dev. 18, 117-125. https://doi.org/10.1101/gad.1165904
  21. Kashiyama, K., Nakazawa, Y., Pilz, D.T., Guo, C., Shimada, M., Sasaki, K., Fawcett, H., Wing, J.F., Lewin, S.O., Carr, L., et al. (2013). Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia. Am. J. Hum. Genet. 92, 807-819. https://doi.org/10.1016/j.ajhg.2013.04.007
  22. Kim, H., and D'Andrea, A.D. (2012). Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway. Genes Dev. 26, 1393-1408. https://doi.org/10.1101/gad.195248.112
  23. Kim, Y., Lach, F.P., Desetty, R., Hanenberg, H., Auerbach, A.D., and Smogorzewska, A. (2011). Mutations of the SLX4 gene in Fanconi anemia. Nat. Genet. 43, 142-146. https://doi.org/10.1038/ng.750
  24. Kim, Y., Spitz, G.S., Veturi, U., Lach, F.P., Auerbach, A.D., and Smogorzewska, A. (2013). Regulation of multiple DNA repair pathways by the Fanconi anemia protein SLX4. Blood 121, 54-63. https://doi.org/10.1182/blood-2012-07-441212
  25. Kottemann, M.C., and Smogorzewska, A. (2013). Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature 493, 356-363. https://doi.org/10.1038/nature11863
  26. Kumaresan, K.R., and Lambert, M.W. (2000). Fanconi anemia, complementation group A, cells are defective in ability to produce incisions at sites of psoralen interstrand cross-links. Carcinogenesis 21, 741-751. https://doi.org/10.1093/carcin/21.4.741
  27. Kuraoka, I., Kobertz, W.R., Ariza, R.R., Biggerstaff, M., Essigmann, J.M., and Wood, R.D. (2000). Repair of an interstrand DNA cross-link initiated by ERCC1-XPF repair/recombination nuclease. J. Biol. Chem. 275, 26632-26636. https://doi.org/10.1074/jbc.C000337200
  28. Li, X., and Heyer, W.D. (2008). Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 18, 99-113. https://doi.org/10.1038/cr.2008.1
  29. Liu, Y., and West, S.C. (2004). Happy Hollidays: 40th anniversary of the Holliday junction. Nat. Rev. Mol. Cell. Biol. 5, 937-944. https://doi.org/10.1038/nrm1502
  30. Matos, J., Blanco, M.G., Maslen, S., Skehel, J.M., and West, S.C. (2011). Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis. Cell 147, 158-172. https://doi.org/10.1016/j.cell.2011.08.032
  31. McPherson, J.P., Lemmers, B., Chahwan, R., Pamidi, A., Migon, E., Matysiak-Zablocki, E., Moynahan, M.E., Essers, J., Hanada, K., Poonepalli, A., et al. (2004). Involvement of mammalian Mus81 in genome integrity and tumor suppression. Science 304, 1822-1826. https://doi.org/10.1126/science.1094557
  32. Mullen, J.R., Kaliraman, V., Ibrahim, S.S., and Brill, S.J. (2001). Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics 157, 103-118.
  33. Munoz, I.M., Hain, K., Declais, A.C., Gardiner, M., Toh, G.W., Sanchez-Pulido, L., Heuckmann, J.M., Toth, R., Macartney, T., Eppink, B., et al. (2009). Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol. Cell 35, 116-127. https://doi.org/10.1016/j.molcel.2009.06.020
  34. Ohouo, P.Y., Bastos de Oliveira, F.M., Almeida, B.S., and Smolka, M.B. (2010). DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response. Mol. Cell 39, 300-306. https://doi.org/10.1016/j.molcel.2010.06.019
  35. Ohouo, P.Y., Bastos de Oliveira, F.M., Liu, Y., Ma, C.J., and Smolka, M.B. (2013). DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9. Nature 493, 120-124.
  36. Rothfuss, A., and Grompe, M. (2004). Repair kinetics of genomic interstrand DNA cross-links: evidence for DNA double-strand break-dependent activation of the Fanconi anemia/BRCA pathway. Mol. Cell. Biol. 24, 123-134. https://doi.org/10.1128/MCB.24.1.123-134.2004
  37. Saito, T.T., Youds, J.L., Boulton, S.J., and Colaiacovo, M.P. (2009). 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. https://doi.org/10.1371/journal.pgen.1000735
  38. Saito, T.T., Lui, D.Y., Kim, H.M., Meyer, K., and Colaiacovo, M.P. (2013). Interplay between structure-specific endonucleases for crossover control during Caenorhabditis elegans meiosis. PLoS Genet. 9, e1003586. https://doi.org/10.1371/journal.pgen.1003586
  39. Smogorzewska, A., van Steensel, B., Bianchi, A., Oelmann, S.,Schaefer, M.R., Schnapp, G., and de Lange, T. (2000). Control of human telomere length by TRF1 and TRF2. Mol. Cell. Biol. 20, 1659-1668. https://doi.org/10.1128/MCB.20.5.1659-1668.2000
  40. Stoepker, C., Hain, K., Schuster, B., Hilhorst-Hofstee, Y., Rooimans, M.A., Steltenpool, J., Oostra, A.B., Eirich, K., Korthof, E.T., Nieuwint, A.W., et al. (2011). SLX4, a coordinator of structurespecific endonucleases, is mutated in a new Fanconi anemia subtype. Nat. Genet. 43, 138-141. https://doi.org/10.1038/ng.751
  41. Sung, P., and Klein, H. (2006). Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat. Rev. Mol. Cell Biol. 7, 739-750. https://doi.org/10.1038/nrm2008
  42. Svendsen, J.M., and Harper, J.W. (2010). GEN1/Yen1 and the SLX4 complex: Solutions to the problem of Holliday junction resolution. Genes Dev. 24, 521-536. https://doi.org/10.1101/gad.1903510
  43. Svendsen, J.M., Smogorzewska, A., Sowa, M.E., O'Connell, B.C., Gygi, S.P., Elledge, S.J., and Harper, J.W. (2009). Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell 138, 63-77. https://doi.org/10.1016/j.cell.2009.06.030
  44. Wan, B., Yin, J., Horvath, K., Sarkar, J., Chen, Y., Wu, J., Wan, K., Lu, J., Gu, P., Yu, E.Y., et al. (2013). SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres. Cell Rep. 4, 861-869. https://doi.org/10.1016/j.celrep.2013.08.017
  45. Wilson, J.S., Tejera, A.M., Castor, D., Toth, R., Blasco, M.A., and Rouse, J. (2013). Localization-dependent and -independent roles of SLX4 in regulating telomeres. Cell Rep. 4, 853-860. https://doi.org/10.1016/j.celrep.2013.07.033
  46. Wu, L., and Hickson, I.D. (2006). DNA helicases required for homologous recombination and repair of damaged replication forks. Ann. Rev. Genet. 40, 279-306. https://doi.org/10.1146/annurev.genet.40.110405.090636
  47. Wyatt, H.D., Sarbajna, S., Matos, J., and West, S.C. (2013). Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells. Mol. Cell 52, 234-247. https://doi.org/10.1016/j.molcel.2013.08.035
  48. Yamamoto, K.N., Kobayashi, S., Tsuda, M., Kurumizaka, H., Takata, M., Kono, K., Jiricny, J., Takeda, S., and Hirota, K. (2011). Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway. Proc. Natl. Acad. Sci. USA 108, 6492-6496. https://doi.org/10.1073/pnas.1018487108

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