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Utilizing Yeast Surface Human Proteome Display Libraries to Identify Small Molecule-Protein Interactions

  • Scott Bidlingmaier
  • Bin Liu
Part of the Methods in Molecular Biology book series (MIMB, volume 1319)

Abstract

The identification of proteins that interact with small bioactive molecules is a critical but often difficult and time-consuming step in understanding cellular signaling pathways or molecular mechanisms of drug action. Numerous methods for identifying small molecule-interacting proteins have been developed and utilized, including affinity-based purification followed by mass spectrometry analysis, protein microarrays, phage display, and three-hybrid approaches. Although all these methods have been used successfully, there remains a need for additional techniques for analyzing small molecule-protein interactions. A promising method for identifying small molecule-protein interactions is affinity-based selection of yeast surface-displayed human proteome libraries. Large and diverse libraries displaying human protein fragments on the surface of yeast cells have been constructed and subjected to FACS-based enrichment followed by comprehensive exon microarray-based output analysis to identify protein fragments with affinity for small molecule ligands. In a recent example, a proteome-wide search has been successfully carried out to identify cellular proteins binding to the signaling lipids PtdIns(4,5)P2 and PtdIns(3,4,5)P3. Known phosphatidylinositide-binding proteins such as pleckstrin homology domains were identified, as well as many novel interactions. Intriguingly, many novel nuclear phosphatidylinositide-binding proteins were discovered. Although the existence of an independent pool of nuclear phosphatidylinositides has been known about for some time, their functions and mechanism of action remain obscure. Thus, the identification and subsequent study of nuclear phosphatidylinositide-binding proteins is expected to bring new insights to this important biological question. Based on the success with phosphatidylinositides, it is expected that the screening of yeast surface-displayed human proteome libraries will be of general use for the discovery of novel small molecule-protein interactions, thus facilitating the study of cellular signaling pathways and mechanisms of drug action or toxicity.

Key words

Yeast cell surface display cDNA library Small molecule-protein interaction Drug-binding protein Small signaling molecule-binding protein Phosphatidylinositides Chromatin remodeling Transcription regulation Homeobox domain-containing protein 

Notes

Acknowledgements

We thank the National Institutes of Health for financial support (R01 CA118919, R01 CA129491, and R01 CA171315).

References

  1. 1.
    Ziegler S, Pries V, Hedberg C, Waldmann H (2013) Target identification for small bioactive molecules: finding the needle in the haystack. Angew Chem Int Ed 52:2744–2792. doi: 10.1002/anie.201208749 CrossRefGoogle Scholar
  2. 2.
    Lomenick B, Olsen RW, Huang J (2011) Identification of direct protein targets of small molecules. ACS Chem Biol 6:34–46. doi: 10.1021/cb100294v PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Raida M (2011) Drug target deconvolution by chemical proteomics. Curr Opin Chem Biol 15:570–575. doi: 10.1016/j.cbpa.2011.06.016 PubMedCrossRefGoogle Scholar
  4. 4.
    Sakamoto S, Hatakeyama M, Ito T, Handa H (2012) Tools and methodologies capable of isolating and identifying a target molecule for a bioactive compound. Bioorg Med Chem 20:1990–2001. doi: 10.1016/j.bmc.2011.12.022 PubMedCrossRefGoogle Scholar
  5. 5.
    Brehmer D, Greff Z, Godl K et al (2005) Cellular targets of gefitinib. Cancer Res 65:379–382PubMedGoogle Scholar
  6. 6.
    Godl K, Gruss OJ, Eickhoff J et al (2005) Proteomic characterization of the angiogenesis inhibitor SU6668 reveals multiple impacts on cellular kinase signaling. Cancer Res 65:6919–6926. doi: 10.1158/0008-5472.CAN-05-0574 PubMedCrossRefGoogle Scholar
  7. 7.
    Bantscheff M, Eberhard D, Abraham Y et al (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol 25:1035–1044. doi: 10.1038/nbt1328 PubMedCrossRefGoogle Scholar
  8. 8.
    Ito T, Ando H, Suzuki T et al (2010) Identification of a primary target of thalidomide teratogenicity. Science 327:1345–1350. doi: 10.1126/science.1177319 PubMedCrossRefGoogle Scholar
  9. 9.
    Reymond Sutandy F, Qian J, Chen C-S, Zhu H (2013) Overview of protein microarrays. Curr Protoc Protein Sci Editor Board John E Coligan Al 0 27:Unit–27.1. doi:  10.1002/0471140864.ps2701s72
  10. 10.
    Chen R, Snyder M (2010) Yeast proteomics and protein microarrays. J Proteomics 73:2147–2157. doi: 10.1016/j.jprot.2010.08.003 PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Berrade L, Garcia AE, Camarero JA (2011) Protein microarrays: novel developments and applications. Pharm Res 28:1480–1499. doi: 10.1007/s11095-010-0325-1 PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Zhu H, Bilgin M, Bangham R et al (2001) Global analysis of protein activities using proteome chips. Science 293:2101–2105. doi: 10.1126/science.1062191 PubMedCrossRefGoogle Scholar
  13. 13.
    Schweitzer B, Predki P, Snyder M (2003) Microarrays to characterize protein interactions on a whole-proteome scale. Proteomics 3:2190–2199. doi: 10.1002/pmic.200300610 PubMedCrossRefGoogle Scholar
  14. 14.
    Huang J, Zhu H, Haggarty SJ et al (2004) Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips. Proc Natl Acad Sci U S A 101:16594–16599. doi: 10.1073/pnas.0407117101 PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Singh J, Salcius M, Liu S-W et al (2008) DcpS as a therapeutic target for spinal muscular atrophy. ACS Chem Biol 3:711–722. doi: 10.1021/cb800120t PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Rodi DJ, Janes RW, Sanganee HJ et al (1999) Screening of a library of phage-displayed peptides identifies human Bcl-2 as a taxol-binding protein. J Mol Biol 285:197–203. doi: 10.1006/jmbi.1998.2303 PubMedCrossRefGoogle Scholar
  17. 17.
    Jin Y, Yu J, Yu YG (2002) Identification of hNopp140 as a binding partner for doxorubicin with a phage display cloning method. Chem Biol 9:157–162. doi: 10.1016/S1074-5521(02)00096-0 PubMedCrossRefGoogle Scholar
  18. 18.
    Van Dorst B, Mehta J, Rouah-Martin E et al (2012) Phage display as a method for discovering cellular targets of small molecules. Methods 58:56–61. doi: 10.1016/j.ymeth.2012.07.011 PubMedCrossRefGoogle Scholar
  19. 19.
    Shim JS, Lee J, Park H-J et al (2004) A new curcumin derivative, HBC, interferes with the cell cycle progression of colon cancer cells via antagonization of the Ca2+/Calmodulin function. Chem Biol 11:1455–1463. doi: 10.1016/j.chembiol.2004.08.015 PubMedCrossRefGoogle Scholar
  20. 20.
    Aoki S, Morohashi K, Sunoki T et al (2007) Screening of paclitaxel-binding molecules from a library of random peptides displayed on T7 phage particles using paclitaxel-photoimmobilized resin. Bioconjug Chem 18:1981–1986. doi: 10.1021/bc700287v PubMedCrossRefGoogle Scholar
  21. 21.
    Takakusagi Y, Kuramochi K, Takagi M et al (2008) Efficient one-cycle affinity selection of binding proteins or peptides specific for a small-molecule using a T7 phage display pool. Bioorg Med Chem 16:9837–9846. doi: 10.1016/j.bmc.2008.09.061 PubMedCrossRefGoogle Scholar
  22. 22.
    Van Dorst B, De Coen W, Blust R, Robbens J (2010) Phage display as a novel screening tool for primary toxicological targets. Environ Toxicol Chem 29:250–255. doi: 10.1002/etc.38 PubMedCrossRefGoogle Scholar
  23. 23.
    Van Dorst B, Mehta J, Rouah-Martin E et al (2010) cDNA phage display as a novel tool to screen for cellular targets of chemical compounds. Toxicol In Vitro 24:1435–1440. doi: 10.1016/j.tiv.2010.04.003 PubMedCrossRefGoogle Scholar
  24. 24.
    Van Dorst B, Mehta J, Rouah-Martin E et al (2011) The identification of cellular targets of 17β estradiol using a lytic (T7) cDNA phage display approach. Toxicol In Vitro 25:388–393. doi: 10.1016/j.tiv.2010.10.012 PubMedCrossRefGoogle Scholar
  25. 25.
    Takami M, Takakusagi Y, Kuramochi K et al (2011) A screening of a library of T7 phage-displayed peptide identifies E2F-4 as an etoposide-binding protein. Molecules 16:4278–4294. doi: 10.3390/molecules16054278 PubMedCrossRefGoogle Scholar
  26. 26.
    Matsumoto Y, Shindo Y, Takakusagi Y et al (2011) Screening of a library of T7 phage-displayed peptides identifies alphaC helix in 14-3-3 protein as a CBP501-binding site. Bioorg Med Chem 19:7049–7056. doi: 10.1016/j.bmc.2011.10.004 PubMedCrossRefGoogle Scholar
  27. 27.
    Manita D, Toba Y, Takakusagi Y et al (2011) Camptothecin (CPT) directly binds to human heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and inhibits the hnRNP A1/topoisomerase I interaction. Bioorg Med Chem 19:7690–7697. doi: 10.1016/j.bmc.2011.09.059 PubMedCrossRefGoogle Scholar
  28. 28.
    Miyano Y, Tsukuda S, Sakimoto I et al (2012) Exploration of the binding proteins of perfluorooctane sulfonate by a T7 phage display screen. Bioorg Med Chem 20:3985–3990. doi: 10.1016/j.bmc.2012.05.016 PubMedCrossRefGoogle Scholar
  29. 29.
    Kusayanagi T, Tsukuda S, Shimura S et al (2012) The antitumor agent doxorubicin binds to Fanconi anemia group F protein. Bioorg Med Chem 20:6248–6255. doi: 10.1016/j.bmc.2012.09.015 PubMedCrossRefGoogle Scholar
  30. 30.
    Tsukuda S, Kusayanagi T, Umeda E et al (2013) Ridaifen B, a tamoxifen derivative, directly binds to Grb10 interacting GYF protein 2. Bioorg Med Chem 21:311–320. doi: 10.1016/j.bmc.2012.10.037 PubMedCrossRefGoogle Scholar
  31. 31.
    Kuroiwa Y, Takakusagi Y, Kusayanagi T et al (2013) Identification and characterization of the direct interaction between methotrexate (MTX) and high-mobility group box 1 (HMGB1) protein. PLoS One 8:e63073. doi: 10.1371/journal.pone.0063073 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Licitra EJ, Liu JO (1996) A three-hybrid system for detecting small ligand-protein receptor interactions. Proc Natl Acad Sci U S A 93:12817–12821PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Rezwan M, Auerbach D (2012) Yeast “N”-hybrid systems for protein–protein and drug–protein interaction discovery. Methods 57:423–429. doi: 10.1016/j.ymeth.2012.06.006 PubMedCrossRefGoogle Scholar
  34. 34.
    Cottier S, Mönig T, Wang Z et al (2011) The yeast three-hybrid system as an experimental platform to identify proteins interacting with small signaling molecules in plant cells: potential and limitations. Plant Physiol 2:101. doi: 10.3389/fpls.2011.00101 Google Scholar
  35. 35.
    Chidley C, Haruki H, Pedersen MG et al (2011) A yeast-based screen reveals that sulfasalazine inhibits tetrahydrobiopterin biosynthesis. Nat Chem Biol 7:375–383. doi: 10.1038/nchembio.557 PubMedCrossRefGoogle Scholar
  36. 36.
    Shepard AR, Conrow RE, Pang I-H et al (2013) Identification of PDE6D as a molecular target of anecortave acetate via a methotrexate-anchored yeast three-hybrid screen. ACS Chem Biol 8:549–558. doi: 10.1021/cb300296m PubMedCrossRefGoogle Scholar
  37. 37.
    Moser S, Johnsson K (2013) Yeast three-hybrid screening for identifying anti-tuberculosis drug targets. Chembiochem 14:2239–2242. doi: 10.1002/cbic.201300472 PubMedCrossRefGoogle Scholar
  38. 38.
    Boder ET, Wittrup KD (1997) Yeast surface display for screening combinatorial polypeptide libraries. Nat Biotechnol 15:553–557. doi: 10.1038/nbt0697-553 PubMedCrossRefGoogle Scholar
  39. 39.
    Bidlingmaier S, Liu B (2006) Construction and application of a yeast surface-displayed human cDNA library to identify post-translational modification-dependent protein-protein interactions. Mol Cell Proteomics 5:533–540. doi: 10.1074/mcp.M500309-MCP200 PubMedCrossRefGoogle Scholar
  40. 40.
    Bidlingmaier S, Liu B (2007) Interrogating yeast surface-displayed human proteome to identify small molecule-binding proteins. Mol Cell Proteomics 6:2012–2020. doi: 10.1074/mcp.M700223-MCP200 PubMedCrossRefGoogle Scholar
  41. 41.
    Bidlingmaier S, He J, Wang Y et al (2009) Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma. Cancer Res 69:1570–1577. doi: 10.1158/0008-5472.CAN-08-1363 PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Bidlingmaier S, Liu B (2011) Construction of yeast surface-displayed cDNA libraries. Methods Mol Biol 729:199–210. doi: 10.1007/978-1-61779-065-2_13 PubMedCentralPubMedGoogle Scholar
  43. 43.
    Bidlingmaier S, Liu B (2011) Identification of protein/target molecule interactions using yeast surface-displayed cDNA libraries. Methods Mol Biol 729:211–223. doi: 10.1007/978-1-61779-065-2_14 PubMedCentralPubMedGoogle Scholar
  44. 44.
    Bidlingmaier S, Wang Y, Liu Y et al (2011) Comprehensive analysis of yeast surface displayed cDNA library selection outputs by exon microarray to identify novel protein-ligand interactions. Mol Cell Proteomics. doi: 10.1074/mcp.M110.005116 PubMedCentralPubMedGoogle Scholar
  45. 45.
    Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–657. doi: 10.1038/nature05185 PubMedCrossRefGoogle Scholar
  46. 46.
    Balla T (2013) Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol Rev 93:1019–1137. doi: 10.1152/physrev.00028.2012 PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Lemmon MA (2008) Membrane recognition by phospholipid-binding domains. Nat Rev Mol Cell Biol 9:99–111. doi: 10.1038/nrm2328 PubMedCrossRefGoogle Scholar
  48. 48.
    McLaughlin S, Murray D (2005) Plasma membrane phosphoinositide organization by protein electrostatics. Nature 438:605–611. doi: 10.1038/nature04398 PubMedCrossRefGoogle Scholar
  49. 49.
    Best MD (2014) Global approaches for the elucidation of phosphoinositide-binding proteins. Chem Phys Lipids. doi: 10.1016/j.chemphyslip.2013.10.014 PubMedGoogle Scholar
  50. 50.
    Ahn J-Y, Liu X, Cheng D et al (2005) Nucleophosmin/B23, a nuclear PI(3,4,5)P3 receptor, mediates the antiapoptotic actions of NGF by inhibiting CAD. Mol Cell 18:435–445. doi: 10.1016/j.molcel.2005.04.010 PubMedCrossRefGoogle Scholar
  51. 51.
    Lewis AE, Sommer L, Arntzen MØ et al (2011) Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction. Mol Cell Proteomics 10:M110.003376. doi: 10.1074/mcp.M110.003376 PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Isakoff SJ, Cardozo T, Andreev J et al (1998) Identification and analysis of PH domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast. EMBO J 17:5374–5387. doi: 10.1093/emboj/17.18.5374 PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Klarlund JK, Guilherme A, Holik JJ et al (1997) Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing Pleckstrin and Sec7 homology domains. Science 275:1927–1930. doi: 10.1126/science.275.5308.1927 PubMedCrossRefGoogle Scholar
  54. 54.
    Jungmichel S, Sylvestersen KB, Choudhary C et al (2014) Specificity and commonality of the phosphoinositide-binding proteome analyzed by quantitative mass spectrometry. Cell Rep 6:578–591. doi: 10.1016/j.celrep.2013.12.038 PubMedCrossRefGoogle Scholar
  55. 55.
    Rao VR, Corradetti MN, Chen J et al (1999) Expression cloning of protein targets for 3-phosphorylated phosphoinositides. J Biol Chem 274:37893–37900PubMedCrossRefGoogle Scholar
  56. 56.
    Shah ZH, Jones DR, Sommer L et al (2013) Nuclear phosphoinositides and their impact on nuclear functions. FEBS J 280:6295–6310. doi: 10.1111/febs.12543 PubMedCrossRefGoogle Scholar
  57. 57.
    Fiume R, Keune WJ, Faenza I et al (2012) Nuclear phosphoinositides: location, regulation and function. In: Balla T, Wymann M, York JD (eds) Phosphoinositides II: diverse biological functions. Springer, Netherlands, pp 335–361CrossRefGoogle Scholar
  58. 58.
    Martelli AM, Ognibene A, Buontempo F et al (2011) Nuclear phosphoinositides and their roles in cell biology and disease. Crit Rev Biochem Mol Biol 46:436–457. doi: 10.3109/10409238.2011.609530 PubMedCrossRefGoogle Scholar
  59. 59.
    Viiri K, Mäki M, Lohi O (2012) Phosphoinositides as regulators of protein-chromatin interactions. Sci Signal 5:pe19. doi: 10.1126/scisignal.2002917 PubMedCrossRefGoogle Scholar
  60. 60.
    Yu H, Fukami K, Watanabe Y et al (1998) Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histone H1. Eur J Biochem 251:281–287. doi: 10.1046/j.1432-1327.1998.2510281.x PubMedCrossRefGoogle Scholar
  61. 61.
    Gozani O, Karuman P, Jones DR et al (2003) The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor. Cell 114:99–111. doi: 10.1016/S0092-8674(03)00480-X PubMedCrossRefGoogle Scholar
  62. 62.
    Krylova IN, Sablin EP, Moore J et al (2005) Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell 120:343–355. doi: 10.1016/j.cell.2005.01.024 PubMedCrossRefGoogle Scholar
  63. 63.
    Li Y, Choi M, Cavey G et al (2005) Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1. Mol Cell 17:491–502. doi: 10.1016/j.molcel.2005.02.002 PubMedCrossRefGoogle Scholar
  64. 64.
    Ortlund EA, Lee Y, Solomon IH et al (2005) Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP. Nat Struct Mol Biol 12:357–363. doi: 10.1038/nsmb910 PubMedCrossRefGoogle Scholar
  65. 65.
    Meerschaert K, Tun MP, Remue E et al (2009) The PDZ2 domain of zonula occludens-1 and -2 is a phosphoinositide binding domain. Cell Mol Life Sci 66:3951–3966. doi: 10.1007/s00018-009-0156-6 PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Viiri KM, Jänis J, Siggers T et al (2009) DNA-binding and -bending activities of SAP30L and SAP30 are mediated by a zinc-dependent module and monophosphoinositides. Mol Cell Biol 29:342–356. doi: 10.1128/MCB.01213-08 PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Toska E, Campbell HA, Shandilya J et al (2012) Repression of transcription by WT1-BASP1 requires the myristoylation of BASP1 and the PIP2-dependent recruitment of histone deacetylase. Cell Rep 2:462–469. doi: 10.1016/j.celrep.2012.08.005 PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Yildirim S, Castano E, Sobol M et al (2013) Involvement of phosphatidylinositol 4,5-bisphosphate in RNA polymerase I transcription. J Cell Sci 126:2730–2739. doi: 10.1242/jcs.123661 PubMedCrossRefGoogle Scholar
  69. 69.
    Gehring WJ, Qian YQ, Billeter M et al (1994) Homeodomain-DNA recognition. Cell 78:211–223PubMedCrossRefGoogle Scholar
  70. 70.
    van Koningsbruggen S, Straasheijm KR, Sterrenburg E et al (2007) FRG1P-mediated aggregation of proteins involved in pre-mRNA processing. Chromosoma 116:53–64. doi: 10.1007/s00412-006-0083-3 PubMedCrossRefGoogle Scholar
  71. 71.
    Loyer P, Trembley JH, Lahti JM, Kidd VJ (1998) The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related PITSLRE protein kinase in vivo. J Cell Sci 111:1495–1506PubMedGoogle Scholar
  72. 72.
    Sapra AK, Änkö M-L, Grishina I et al (2009) SR protein family members display diverse activities in the formation of nascent and mature mRNPs in vivo. Mol Cell 34:179–190. doi: 10.1016/j.molcel.2009.02.031 PubMedCrossRefGoogle Scholar
  73. 73.
    Cowper AE, Cáceres JF, Mayeda A, Screaton GR (2001) Serine-Arginine (SR) protein-like factors that antagonize authentic SR proteins and regulate alternative splicing. J Biol Chem 276:48908–48914. doi: 10.1074/jbc.M103967200 PubMedCrossRefGoogle Scholar
  74. 74.
    Osborne SL, Thomas CL, Gschmeissner S, Schiavo G (2001) Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing. J Cell Sci 114:2501–2511PubMedGoogle Scholar
  75. 75.
    Watt S, Kular G, Fleming I et al (2002) Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the pleckstrin homology domain of phospholipase C δ1. http://www.biochemj.org/bj/363/0657/bj3630657.htm. Accessed 3 May 2014
  76. 76.
    Boronenkov IV, Loijens JC, Umeda M, Anderson RA (1998) Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol Biol Cell 9:3547–3560. doi: 10.1091/mbc.9.12.3547 PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Spector DL, Lamond AI (2011) Nuclear speckles. Cold Spring Harb Perspect Biol 3:a000646. doi: 10.1101/cshperspect.a000646 PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Mortier E, Wuytens G, Leenaerts I et al (2005) Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions. EMBO J 24:2556–2565. doi: 10.1038/sj.emboj.7600722 PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Wang Z, Castaño IB, Peñas ADL et al (2000) Pol κ: a DNA polymerase required for sister chromatid cohesion. Science 289:774–779. doi: 10.1126/science.289.5480.774 PubMedCrossRefGoogle Scholar
  80. 80.
    Wang Z, Castaño IB, Adams C et al (2002) Structure/function analysis of the Saccharomyces cerevisiae Trf4/Pol sigma DNA polymerase. Genetics 160:381–391PubMedCentralPubMedGoogle Scholar
  81. 81.
    Kumar A, Fernandez-Capetillo O, Carrera AC (2010) Nuclear phosphoinositide 3-kinase β controls double-strand break DNA repair. Proc Natl Acad Sci 107:7491–7496. doi: 10.1073/pnas.0914242107 PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Shirakawa H, Herrera JE, Bustin M, Postnikov Y (2000) Targeting of high mobility group-14/-17 proteins in chromatin is independent of DNA sequence. J Biol Chem 275:37937–37944. doi: 10.1074/jbc.M000989200 PubMedCrossRefGoogle Scholar
  83. 83.
    Crippa MP, Trieschmann L, Alfonso PJ et al (1993) Deposition of chromosomal protein HMG-17 during replication affects the nucleosomal ladder and transcriptional potential of nascent chromatin. EMBO J 12:3855–3864PubMedCentralPubMedGoogle Scholar
  84. 84.
    Tremethick DJ, Hyman L (1996) High mobility group protein 14 and 17 can prevent the close packing of nucleosomes by increasing the strength of protein contacts in the linker DNA. J Biol Chem 271:12009–12016PubMedCrossRefGoogle Scholar
  85. 85.
    Trieschmann L, Alfonso PJ, Crippa MP et al (1995) Incorporation of chromosomal proteins HMG-14/HMG-17 into nascent nucleosomes induces an extended chromatin conformation and enhances the utilization of active transcription complexes. EMBO J 14:1478–1489PubMedCentralPubMedGoogle Scholar
  86. 86.
    Vestner B, Bustin M, Gruss C (1998) Stimulation of replication efficiency of a chromatin template by chromosomal protein HMG-17. J Biol Chem 273:9409–9414PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California San FranciscoSan FranciscoUSA

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