DOI QR코드

DOI QR Code

Stimulation of Oligonucleotide-Directed Gene Correction by Redβ Expression and MSH2 Depletion in Human HT1080 Cells

  • Xu, Ke (Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital) ;
  • Stewart, A. Francis (Genomics, Bio Innovations Zentrum, Technische Universitaet Dresden) ;
  • Porter, Andrew C.G. (Gene Targeting Group, Department of Hematology, Faculty of Medicine, Imperial College London)
  • Received : 2014.06.10
  • Accepted : 2014.10.15
  • Published : 2015.01.31

Abstract

The correction of disease-causing mutations by single-strand oligonucleotide-templated DNA repair (ssOR) is an attractive approach to gene therapy, but major improvements in ssOR efficiency and consistency are needed. The mechanism of ssOR is poorly understood but may involve annealing of oligonucleotides to transiently exposed single-stranded regions in the target duplex. In bacteria and yeast it has been shown that ssOR is promoted by expression of $Red{\beta}$, a single-strand DNA annealing protein from bacteriophage lambda. Here we show that $Red{\beta}$ expression is well tolerated in a human cell line where it consistently promotes ssOR. By use of short interfering RNA, we also show that ssOR is stimulated by the transient depletion of the endogenous DNA mismatch repair protein MSH2. Furthermore, we find that the effects of $Red{\beta}$ expression and MSH2 depletion on ssOR can be combined with a degree of cooperativity. These results suggest that oligonucleotide annealing and mismatch recognition are distinct but interdependent events in ssOR that can be usefully modulated in gene correction strategies.

Keywords

DNA repair;gene correction;mismatch repair;$Red{\beta}$;single-strand oligonucleotide

Acknowledgement

Supported by : National Natural Science Foundation of China

References

  1. Aarts, M., and te Riele, H. (2011). Progress and prospects: oligonucleotide-directed gene modification in mouse embryonic stem cells: a route to therapeutic application. Gene Ther. 18, 213-219. https://doi.org/10.1038/gt.2010.161
  2. Aarts, M., Dekker, M., de Vries, S., van der Wal, A., and te Riele, H. (2006). Generation of a mouse mutant by oligonucleotidemediated gene modification in ES cells. Nucleic Acids Res. 34, e147. https://doi.org/10.1093/nar/gkl896
  3. Andersen, M.S., Sorensen, C.B., Bolund, L., and Jensen, T.G. (2002). Mechanisms underlying targeted gene correction using chimeric RNA/DNA and single-stranded DNA oligonucleotides. J. Mol. Med. (Berl). 80, 770-781. https://doi.org/10.1007/s00109-002-0393-8
  4. Andrieu-Soler, C., Casas, M., Faussat, A.-M., Gandolphe, C., Doat, M., Tempe, D., Giovannangeli, C., Behar-Cohen, F., and Concordet, J.-P. (2005). Stable transmission of targeted gene modification using single-stranded oligonucleotides with flanking LNAs. Nucleic Acids Res. 33, 3733-3742. https://doi.org/10.1093/nar/gki686
  5. Bochkarev, A., and Bochkareva, E. (2004). From RPA to BRCA2: lessons from single-stranded DNA binding by the OB-fold. Curr. Opin. Struct. Biol. 14, 36-42. https://doi.org/10.1016/j.sbi.2004.01.001
  6. Brachman, E.E., and Kmiec, E.B. (2003). Targeted nucleotide repair of cyc1 mutations in Saccharomyces cerevisiae directed by modified single-stranded DNA oligonucleotides. Genetics 163, 527-538.
  7. Brachman, E.E., and Kmiec, E.B. (2005). Gene repair in mammalian cells is stimulated by the elongation of S phase and transient stalling of replication forks. DNA Repair (Amst). 4, 445-457. https://doi.org/10.1016/j.dnarep.2004.11.007
  8. Brough, R., Frankum, J.R., Costa-Cabral, S., Lord, C.J., and Ashworth, A. (2011). Searching for synthetic lethality in cancer. Curr. Opin. Genet. Dev. 21, 34-41. https://doi.org/10.1016/j.gde.2010.10.009
  9. Chen, F., Pruett-Miller, S.M., Huang, Y., Gjoka, M., Duda, K., Taunton, J., Collingwood, T.N., Frodin, M., and Davis, G.D. (2011). Highfrequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. Nat. Methods 8, 753-755. https://doi.org/10.1038/nmeth.1653
  10. Costantino, N., and Court, D.L. (2003). Enhanced levels of lambda Red-mediated recombinants in mismatch repair mutants. Proc. Natl. Acad. Sci. USA 100, 15748-15753. https://doi.org/10.1073/pnas.2434959100
  11. Court, D.L., Sawitzke, J. a, and Thomason, L.C. (2002). Genetic engineering using homologous recombination. Annu. Rev. Genet. 36, 361-388. https://doi.org/10.1146/annurev.genet.36.061102.093104
  12. Dekker, M., Brouwers, C., and te Riele, H. (2003). Targeted gene modification in mismatch-repair-deficient embryonic stem cells by single-stranded DNA oligonucleotides. Nucleic Acids Res. 31,e27. https://doi.org/10.1093/nar/gng027
  13. Deng, C., and Capecchi, M.R. (1992). Reexamination of gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus. Mol. Cell. Biol. 12, 3365-3371. https://doi.org/10.1128/MCB.12.8.3365
  14. Ellis, H.M., Yu, D., DiTizio, T., and Court, D.L. (2001). High efficiency mutagenesis, repair, and engineering of chromosomal DNA using single-stranded oligonucleotides. Proc. Natl. Acad. Sci. USA 98, 6742-6746. https://doi.org/10.1073/pnas.121164898
  15. Erler, A., Wegmann, S., Elie-Caille, C., Bradshaw, C.R., Maresca, M., Seidel, R., Habermann, B., Muller, D.J., and Stewart, A.F. (2009). Conformational adaptability of Redbeta during DNA annealing and implications for its structural relationship with Rad52. J. Mol. Biol. 391, 586-598. https://doi.org/10.1016/j.jmb.2009.06.030
  16. Ferrara, L., and Kmiec, E.B. (2004). Camptothecin enhances the frequency of oligonucleotide-directed gene repair in mammalian cells by inducing DNA damage and activating homologous recombination. Nucleic Acids Res. 32, 5239-5248. https://doi.org/10.1093/nar/gkh822
  17. Gaj, T., Gersbach, C. a, and Barbas, C.F. (2013). 2012 ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 31, 397-405. https://doi.org/10.1016/j.tibtech.2013.04.004
  18. Hu, Y., Parekh-Olmedo, H., Drury, M., Skogen, M., and Kmiec, E.B. (2005). Reaction parameters of targeted gene repair in mammalian cells. Mol. Biotechnol. 29, 197-210. https://doi.org/10.1385/MB:29:3:197
  19. Humbert, O., Davis, L., and Maizels, N. (2012). Targeted gene therapies: tools, applications, optimization. Crit. Rev. Biochem. Mol. Biol. 47, 264-281. https://doi.org/10.3109/10409238.2012.658112
  20. Igoucheva, O., Alexeev, V., and Yoon, K. (2001). Targeted gene correction by small single-stranded oligonucleotides in mammalian cells. Gene Ther. 8, 391-399. https://doi.org/10.1038/sj.gt.3301414
  21. Igoucheva, O., Alexeev, V., Pryce, M., and Yoon, K. (2003). Transcription affects formation and processing of intermediates in oligonucleotide-mediated gene alteration. Nucleic Acids Res. 31, 2659-2670. https://doi.org/10.1093/nar/gkg360
  22. Igoucheva, O., Alexeev, V., and Yoon, K. (2004). Oligonucleotidedirected mutagenesis and targeted gene correction: a mechanistic point of view. Curr. Mol. Med. 4, 445-463. https://doi.org/10.2174/1566524043360465
  23. Itzhaki, J.E., Gilbert, C.S., and Porter, A.C. (1997). Construction by gene targeting in human cells of a "conditional" CDC2 mutant that rereplicates its DNA. Nat. Genet. 15, 258-265. https://doi.org/10.1038/ng0397-258
  24. Iyer, L.M., Koonin, E. V, and Aravind, L. (2002). Classification and evolutionary history of the single-strand annealing proteins, RecT, Redbeta, ERF and RAD52. BMC Genomics 3, 8. https://doi.org/10.1186/1471-2164-3-8
  25. Jiricny J. (2006). The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. 7, 335-346.
  26. Karakousis, G., Ye, N., Li, Z., Chiu, S.K., Reddy, G., and Radding, C.M. (1998). The beta protein of phage lambda binds preferentially to an intermediate in DNA renaturation. J. Mol. Biol. 276, 721-731. https://doi.org/10.1006/jmbi.1997.1573
  27. Kenner, O., Kneisel, A., Klingler, J., Bartelt, B., Speit, G., Vogel, W., and Kaufmann, D. (2002). Targeted gene correction of hprt mutations by 45 base single-stranded oligonucleotides. Biochem. Biophys. Res. Commun. 299, 787-792. https://doi.org/10.1016/S0006-291X(02)02749-3
  28. Khan, I.F., Hirata, R.K., and Russell, D.W. (2011). AAV-mediated gene targeting methods for human cells. Nat. Protoc. 6, 482-501. https://doi.org/10.1038/nprot.2011.301
  29. Li, Z., Karakousis, G., Chiu, S.K., Reddy, G., and Radding, C.M. (1998). The beta protein of phage lambda promotes strand exchange. J. Mol. Biol. 276, 733-744. https://doi.org/10.1006/jmbi.1997.1572
  30. Li, X., Costantino, N., Lu, L., Liu, D., Watt, R.M., Cheah, K.S.E., Court, D.L., and Huang, J.-D. (2003). Identification of factors influencing strand bias in oligonucleotide-mediated recombination in Escherichia coli. Nucleic Acids Res. 31, 6674-6687. https://doi.org/10.1093/nar/gkg844
  31. Lisby, M., and Rothstein, R. (2009). Choreography of recombination proteins during the DNA damage response. DNA Repair (Amst). 8, 1068-1076. https://doi.org/10.1016/j.dnarep.2009.04.007
  32. Liu, L., Parekh-Olmedo, H., and Kmiec, E.B. (2003). The development and regulation of gene repair. Nat. Rev. Genet. 4, 679-689.
  33. Liu, B., Wu, X., Liu, B., Wang, C., Liu, Y., Zhou, Q., and Xu, K. (2012). MiR-26a enhances metastasis potential of lung cancer cells via AKT pathway by targeting PTEN. Biochim. Biophys. Acta 1822, 1692-1704. https://doi.org/10.1016/j.bbadis.2012.07.019
  34. Majumdar, A., Muniandy, P. a, Liu, J., Liu, J., Liu, S., Cuenoud, B., and Seidman, M.M. (2008). Targeted gene knock in and sequence modulation mediated by a psoralen-linked triplexforming oligonucleotide. J. Biol. Chem. 283, 11244-11252. https://doi.org/10.1074/jbc.M800607200
  35. Manzano, A., Mohri, Z., Sperber, G., Ogris, M., Graham, I., Dickson, G., and Owen, J.S. (2003). Failure to generate atheroprotective apolipoprotein AI phenotypes using synthetic RNA/DNA oligonucleotides (chimeraplasts). J. Gene Med. 5, 795-802. https://doi.org/10.1002/jgm.403
  36. McLachlan, J., Fernandez, S., Helleday, T., and Bryant, H.E. (2009). Specific targeted gene repair using single-stranded DNA oligonucleotides at an endogenous locus in mammalian cells uses homologous recombination. DNA Repair (Amst). 8, 1424-1433. https://doi.org/10.1016/j.dnarep.2009.09.014
  37. Morozov, V., and Wawrousek, E.F. (2008). Single-strand DNAmediated targeted mutagenesis of genomic DNA in early mouse embryos is stimulated by Rad51/54 and by Ku70/86 inhibition. Gene Ther. 15, 468-472. https://doi.org/10.1038/sj.gt.3303088
  38. Muyrers, J.P., Zhang, Y., Buchholz, F., and Stewart, A.F. (2000). RecE/RecT and Redalpha/Redbeta initiate double-stranded break repair by specifically interacting with their respective partners. Genes Dev. 14, 1971-1982.
  39. Nickerson, H.D., and Colledge, W.H. (2003). A comparison of gene repair strategies in cell culture using a lacZ reporter system. Gene Ther. 10, 1584-1591. https://doi.org/10.1038/sj.gt.3302049
  40. Olsen, P.A., Randol, M., and Krauss, S. (2005). Implications of cell cycle progression on functional sequence correction by short single-stranded DNA oligonucleotides. Gene Ther. 12, 546-551. https://doi.org/10.1038/sj.gt.3302454
  41. Papaioannou, I., Simons, J.P., and Owen, J.S. (2012). Oligonucleotide- directed gene-editing technology: mechanisms and future prospects. Expert Opin. Biol. Ther. 12, 329-342. https://doi.org/10.1517/14712598.2012.660522
  42. Pierce, E.A., Liu, Q., Igoucheva, O., Omarrudin, R., Ma, H., Diamond, S.L., and Yoon, K. (2003). Oligonucleotide-directed single-base DNA alterations in mouse embryonic stem cells. Gene Ther. 10, 24-33. https://doi.org/10.1038/sj.gt.3301857
  43. Porter, A.C., and Itzhaki, J.E. (1993). Gene targeting in human somatic cells. Complete inactivation of an interferon-inducible gene. Eur. J. Biochem. 218, 273-281. https://doi.org/10.1111/j.1432-1033.1993.tb18375.x
  44. Radecke, F., Peter, I., Radecke, S., Gellhaus, K., Schwarz, K., and Cathomen, T. (2006). Targeted chromosomal gene modification in human cells by single-stranded oligodeoxynucleotides in the presence of a DNA double-strand break. Mol. Ther. 14, 798-808. https://doi.org/10.1016/j.ymthe.2006.06.008
  45. Radecke, S., Radecke, F., Cathomen, T., and Schwarz, K. (2010). Zinc-finger nuclease-induced gene repair with oligodeoxynu cleotides: wanted and unwanted target locus modifications. Mol. Ther. 18, 743-753. https://doi.org/10.1038/mt.2009.304
  46. Shevelev, I. V, and Hubscher, U. (2002). The 3' 5' exonucleases. Nat. Rev. Mol. Cell Biol. 3, 364-376. https://doi.org/10.1038/nrm804
  47. Swaminathan, S., Ellis, H.M., Waters, L.S., Yu, D., Lee, E.C., Court, D.L., and Sharan, S.K. (2001). Rapid engineering of bacterial artificial chromosomes using oligonucleotides. Genesis 29, 14-21.
  48. Taubes, G. (2002). Gene therapy. The strange case of chimeraplasty. Science 298, 2116-2120. https://doi.org/10.1126/science.298.5601.2116
  49. Urnov, F.D., Miller, J.C., Lee, Y.-L., Beausejour, C.M., Rock, J.M., Augustus, S., Jamieson, A.C., Porteus, M.H., Gregory, P.D., and Holmes, M.C. (2005). Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435, 646-651. https://doi.org/10.1038/nature03556
  50. Wu, X.-S., Xin, L., Yin, W.-X., Shang, X.-Y., Lu, L., Watt, R.M., Cheah, K.S.E., Huang, J.-D., Liu, D.-P., and Liang, C.-C. (2005). Increased efficiency of oligonucleotide-mediated gene repair through slowing replication fork progression. Proc. Natl. Acad. Sci. USA 102, 2508-2513. https://doi.org/10.1073/pnas.0406991102
  51. Yanez, R.J., and Porter, A.C. (1998). Therapeutic gene targeting. Gene Ther. 5, 149-159. https://doi.org/10.1038/sj.gt.3300601
  52. Zhang, Y., Muyrers, J.P.P., Rientjes, J., and Stewart, A.F. (2003). Phage annealing proteins promote oligonucleotide-directed mutagenesis in Escherichia coli and mouse ES cells. BMC Mol. Biol. 4, 1. https://doi.org/10.1186/1471-2199-4-1