摘要
核苷酸酶是一个非常重要的水解酶家族,它们能够将核苷单磷酸水解成核苷和磷酸根离子,与核苷酸激酶所参与的生物学过程互补,以保证细胞内核苷单磷酸库的平衡。作为一类生命基本活动所必需的酶,核苷酸酶参与了转录,翻译和信号转导等一系列的生物学过程中,从原核生物到真核生物体内都发现了这类酶的存在。从分类学的角度来说,核苷酸酶一般都属于HAD(Haloalkanoate dehalogenase)水解酶大家族,SDT1是一种酿酒酵母源的高度特异性的嘧啶核苷酸酶,参与到酵母的转录过程中。我们表达纯化了SDT1的全长和截去N端的蛋白,并解析了截去N端的蛋白的晶体结构。通过结构分析我们发现,SDT1由帽子结构域和核心结构域两部分组成,两个结构域共同形成了一个经典的α/βRossmann桶的折叠花样,已经解析的HAD水解酶大家族成员一般都采取这种折叠花样。而酶活中心也正是位于这两个结构域之间。进一步,通过浸泡底物的方法,得到了底物和SDT1的复合物结构。通过对复合物的结构解析,我们解释了SDT1的底物特异性的特点,对酶活的机制也有了更深的理解,为进一步酶抑制剂和嘧啶特异性的核苷酸酶抗性药物设计提供了结构基础。
真核生物的转录是一个高度保守的生物学过程, RNA聚合酶II是整个转录过程中起中心角色的蛋白质分子。RNA聚合酶II通过与一系列的辅助因子相互作用,调节着转录的起始、延伸、暂停和终止。RNA聚合酶II相关蛋白1复合物PAF1(RNA Polymerase-Associated Factor 1)在转录的全过程中都结合在RNA聚合酶II上,发挥重要的作用。作为PAF1复合物最早被发现的两个组分之一,CDC73参与到许多转录相关的过程中:结合到RNA聚合酶II上,招募和激活组蛋白调节因子以及其它转录激活因子的信号转导。然而到目前为止,PAF1以及CDC73在转录过程中发挥作用的具体机制并不清楚。我们表达纯化了酿酒酵母源的CDC73全长蛋白和C端结构域片断,并解析了C端结构域的晶体结构。通过结构分析发现,CDC73蛋白的C端结构域折叠成一个类似于小G蛋白的结构花样。虽然在后续的实验中,我们无法检测到CDC73的GTPase活性,但为进一步探索CDC73和PAF1复合物的内在作用机理提供一些线索和结构基础。
The 5’-nucleotidases catalyze the dephosphorylation of ribo- and deoxyribonucleoside monophosphates to the corresponding nucleosides. These enzymes can counteract the activity of nucleoside kinases and compete with other enzymes that consume the nucleoside monophosphates, which balance NTP and dNTP pools in cell. SDT1,first found as the deletion inhibitory factor of transcription elongation factor TFIIS in S. cerevisiae, suppresses the damage induced by deletion of TFIIS by overexpression. Here we report the 1.9? crystal structure of the yeast SDT1 complexed with phosphate and magnesium ions. We also present a 1.7 ? crystal structure of D61A variant complexed with the optimal substrate U5P (uridine 5’-monophosphate). The native SDT1 shows a classic HAD enzymes superfamily structure. The D61A variant structure enables us to characterize that the enzyme’s specificity for the ribo- form of nucleoside 5’-monophosphate is contributed to Asp-63, Asp-130 and Tyr-193.
The yeast Paf1 complex (Paf1C), composed of the proteins Paf1, Cdc73, Ctr9, Leo1, and Rtf1, associates with RNA polymerase II (pol II) from the promoter to the 3′end formation site of mRNA encoding genes. As one component of the first two identified subunits of the Paf1 complex, Cdc73_Yeast (yCdc73) takes part in many transcription related processes including: binding to the RNA polymerase II; recruitment and activation of histone modification factors; communication with other transcriptional activators. The human homolog of yCdc73, also called as parafibromin, is identified as a tumor suppressor linked to breast, renal and gastric cancer. However, the functional mechanism of Cdc73 is not clear until recently. Here, we show the 2.1? crystal structure of the highly conserved C-terminal region of yCdc73. It reveals that Cdc73 appears as a GTPase-like fold. We hope that our found sheds new light on the function modes of cdc73 and Paf1 complex.
引文
(1994). "The CCP4 suite: programs for protein crystallography." Acta Crystallogr D Biol Crystallogr 50(Pt 5): 760-3.
Adams, P. D., R. W. Grosse-Kunstleve, et al. (2002). "PHENIX: building new software for automated crystallographic structure determination." Acta Crystallogr D Biol Crystallogr 58(Pt 11): 1948-54.
AGW, L. (1992). "Recent changes to the MOSFLM package for processing film and image plate data." Joint CCP4 1 ESF-EAMCB Newsletter on Protein Crystallography 26.
Ahmadian, M. R., P. Stege, et al. (1997). "Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras." Nat Struct Biol 4(9): 686-9.
Allegrini, S., A. Scaloni, et al. (2001). "Bovine cytosolic 5'-nucleotidase acts through the formation of an aspartate 52-phosphoenzyme intermediate." J Biol Chem 276(36): 33526-32.
Amici, A., M. Emanuelli, et al. (1997). "Pyrimidine nucleotidases from human erythrocyte possess phosphotransferase activities specific for pyrimidine nucleotides." FEBS Lett 419(2-3): 263-7.
Anantharaman, V., L. Aravind, et al. (2003). "Emergence of diverse biochemical activities in evolutionarily conserved structural scaffolds of proteins." Curr Opin Chem Biol 7(1): 12-20.
Aravind, L., V. Anantharaman, et al. (2002). "Monophyly of class I aminoacyl tRNA synthetase, USPA, ETFP, photolyase, and PP-ATPase nucleotide-binding domains: implications for protein evolution in the RNA." Proteins 48(1): 1-14.
Aravind, L., M. Y. Galperin, et al. (1998). "The catalytic domain of the P-type ATPase has the haloacid dehalogenase fold." Trends Biochem Sci 23(4): 127-9.
Aravind, L. and E. V. Koonin (1998). "A novel family of predicted phosphoesterases includes Drosophila prune protein and bacterial RecJ exonuclease." Trends Biochem Sci 23(1): 17-9.
Aravind, L., D. D. Leipe, et al. (1998). "Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins." Nucleic Acids Res 26(18): 4205-13.
Baker, A. S., M. J. Ciocci, et al. (1998). "Insights into the mechanism of catalysis by the P-C bond-cleaving enzyme phosphonoacetaldehyde hydrolase derived from gene sequence analysis and mutagenesis." Biochemistry 37(26): 9305-15.
Bianchi, V., E. Pontis, et al. (1986). "Interrelations between substrate cycles and de novo synthesis of pyrimidine deoxyribonucleoside triphosphates in 3T6 cells." Proc Natl Acad Sci U S A 83(4): 986-90.
Bitto, E., C. A. Bingman, et al. (2006). "Structure of pyrimidine 5'-nucleotidase type 1. Insight into mechanism of action and inhibition during lead poisoning." J Biol Chem 281(29):20521-9.
Brewster, N. K., G. C. Johnston, et al. (2001). "A bipartite yeast SSRP1 analog comprised of Pob3 and Nhp6 proteins modulates transcription." Mol Cell Biol 21(10): 3491-502.
Clissold, P. M. and C. P. Ponting (2000). "PIN domains in nonsense-mediated mRNA decay and RNAi." Curr Biol 10(24): R888-90.
Collet, J. F., V. Stroobant, et al. (1998). "A new class of phosphotransferases phosphorylated on an aspartate residue in an amino-terminal DXDX(T/V) motif." J Biol Chem 273(23): 14107-12.
Costa, P. J. and K. M. Arndt (2000). "Synthetic lethal interactions suggest a role for the Saccharomyces cerevisiae Rtf1 protein in transcription elongation." Genetics 156(2): 535-47.
Davis, I. W., A. Leaver-Fay, et al. (2007). "MolProbity: all-atom contacts and structure validation for proteins and nucleic acids." Nucleic Acids Res 35(Web Server issue): W375-83.
Emsley, P. and K. Cowtan (2004). "Coot: model-building tools for molecular graphics." Acta Crystallogr D Biol Crystallogr 60(Pt 12 Pt 1): 2126-32.
Evans, P. R. (1993). "in Data Reduction Proceedings of CCP4 Study Weekend." on Data Collection and Processing,Warrington: Daresbury Laboratory pp. 114-122.
Exinger, F. and F. Lacroute (1992). "6-Azauracil inhibition of GTP biosynthesis in Saccharomyces cerevisiae." Curr Genet 22(1): 9-11.
Finnin, M. S., J. R. Donigian, et al. (1999). "Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors." Nature 401(6749): 188-93.
Garvey, E. P., G. T. Lowen, et al. (1998). "Nucleotide and nucleoside analogues as inhibitors of cytosolic 5'-nucleotidase I from heart." Biochemistry 37(25): 9043-51.
Gouet, P., E. Courcelle, et al. (1999). "ESPript: analysis of multiple sequence alignments in PostScript." Bioinformatics 15(4): 305-8.
Gutensohn, W., R. Resta, et al. (1995). "Ecto-5'-nucleotidase activity is not required for T cell activation through CD73." Cell Immunol 161(2): 213-7.
Hisano, T., Y. Hata, et al. (1996). "Crystal structure of L-2-haloacid dehalogenase from Pseudomonas sp. YL. An alpha/beta hydrolase structure that is different from the alpha/beta hydrolase fold." J Biol Chem 271(34): 20322-30.
Holm, L. and C. Sander (1995). "Dali: a network tool for protein structure comparison." Trends Biochem Sci 20(11): 478-80.
Hunsucker, S. A., B. S. Mitchell, et al. (2005). "The 5'-nucleotidases as regulators of nucleotide and drug metabolism." Pharmacol Ther 107(1): 1-30.
Hunsucker, S. A., J. Spychala, et al. (2001). "Human cytosolic 5'-nucleotidase I: characterization and role in nucleoside analog resistance." J Biol Chem 276(13): 10498-504.
Iyer, L. M. and L. Aravind (2002). "The catalytic domains of thiamine triphosphatase and CyaB-like adenylyl cyclase define a novel superfamily of domains that bind organic phosphates." BMC Genomics 3(1): 33.
Kim, Y., A. F. Yakunin, et al. (2004). "Structure- and function-based characterization of a new phosphoglycolate phosphatase from Thermoplasma acidophilum." J Biol Chem 279(1): 517-26.
Knofel, T. and N. Strater (1999). "X-ray structure of the Escherichia coli periplasmic 5'-nucleotidase containing a dimetal catalytic site." Nat Struct Biol 6(5): 448-53.
Knofel, T. and N. Strater (2001). "Mechanism of hydrolysis of phosphate esters by the dimetal center of 5'-nucleotidase based on crystal structures." J Mol Biol 309(1): 239-54.
Koonin, E. V. and R. L. Tatusov (1994). "Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search." J Mol Biol 244(1): 125-32.
Kurihara, T., J. Q. Liu, et al. (1995). "Comprehensive site-directed mutagenesis of L-2-halo acid dehalogenase to probe catalytic amino acid residues." J Biochem 117(6): 1317-22.
Lahiri, S. D., G. Zhang, et al. (2002). "Caught in the act: the structure of phosphorylated beta-phosphoglucomutase from Lactococcus lactis." Biochemistry 41(26): 8351-9.
Lahiri, S. D., G. Zhang, et al. (2003). "The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction." Science 299(5615): 2067-71.
Larkin, M. A., G. Blackshields, et al. (2007). "Clustal W and Clustal X version 2.0." Bioinformatics 23(21): 2947-8.
Laskowski RA, Macarthur MW, et al. (1993). "Procheck—a program to check the stereochemical quality of protein structures." J Appl Crystallogr 26(283–291).
Li, Y. F., Y. Hata, et al. (1998). "Crystal structures of reaction intermediates of L-2-haloacid dehalogenase and implications for the reaction mechanism." J Biol Chem 273(24): 15035-44.
Lowe, J. and L. A. Amos (1998). "Crystal structure of the bacterial cell-division protein FtsZ." Nature 391(6663): 203-6.
Martin, J. L. and F. M. McMillan (2002). "SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold." Curr Opin Struct Biol 12(6): 783-93.
Morais, M. C., W. Zhang, et al. (2000). "The crystal structure of bacillus cereus phosphonoacetaldehyde hydrolase: insight into catalysis of phosphorus bond cleavage and catalytic diversification within the HAD enzyme superfamily." Biochemistry 39(34): 10385-96.
Murshudov, G. N., A. A. Vagin, et al. (1997). "Refinement of macromolecular structures by the maximum-likelihood method." Acta Crystallogr D Biol Crystallogr 53(Pt 3): 240-55.
Nakanishi, T., A. Nakano, et al. (1992). "Purification, gene cloning, and gene disruption of the transcription elongation factor S-II in Saccharomyces cerevisiae." J Biol Chem 267(19): 13200-4.
Nakanishi, T. and K. Sekimizu (2002). "SDT1/SSM1, a multicopy suppressor of S-II null mutant, encodes a novel pyrimidine 5'-nucleotidase." J Biol Chem 277(24): 22103-6.
Olsen, D. B., T. W. Hepburn, et al. (1988). "Investigation of the Bacillus cereus phosphonoacetaldehyde hydrolase. Evidence for a Schiff base mechanism and sequence analysis of an active-site peptide containing the catalytic lysine residue." Biochemistry 27(6): 2229-34.
Otwinowski Z and W. Minor (1997). "Processing of X-ray diffraction data collected in oscillation mode." Macromol Crystallogr 276(307–326).
Peisach, E., J. D. Selengut, et al. (2004). "X-ray crystal structure of the hypothetical phosphotyrosine phosphatase MDP-1 of the haloacid dehalogenase superfamily." Biochemistry 43(40): 12770-9.
Qian, N., G. A. Stanley, et al. (1994). "Purification and characterization of two phosphoglucomutases from Lactococcus lactis subsp. lactis and their regulation in maltose- and glucose-utilizing cells." J Bacteriol 176(17): 5304-11.
Ridder, I. S., H. J. Rozeboom, et al. (1999). "Crystal structures of intermediates in the dehalogenation of haloalkanoates by L-2-haloacid dehalogenase." J Biol Chem 274(43): 30672-8.
Rinaldo-Matthis, A., C. Rampazzo, et al. (2002). "Crystal structure of a human mitochondrial deoxyribonucleotidase." Nat Struct Biol 9(10): 779-87.
Robinson, V. L., D. R. Buckler, et al. (2000). "A tale of two components: a novel kinase and a regulatory switch." Nat Struct Biol 7(8): 626-33.
Rossmann, M. G., D. Moras, et al. (1974). "Chemical and biological evolution of nucleotide-binding protein." Nature 250(463): 194-9.
Shimoaraiso, M., T. Nakanishi, et al. (2000). "Transcription elongation factor S-II confers yeast resistance to 6-azauracil by enhancing expression of the SSM1 gene." J Biol Chem 275(38): 29623-7.
Shin, D. H., A. Roberts, et al. (2003). "Crystal structure of a phosphatase with a unique substrate binding domain from Thermotoga maritima." Protein Sci 12(7): 1464-72.
Strater, N. (2006). "Ecto-5'-nucleotidase: Structure function relationships." Purinergic Signal 2(2): 343-50.
Terwilliger, T. C. (2000). "Maximum-likelihood density modification." Acta Crystallogr D Biol Crystallogr 56(Pt 8): 965-72.
Terwilliger, T. C. and J. Berendzen (1999). "Automated MAD and MIR structure solution." Acta Crystallogr D Biol Crystallogr 55(Pt 4): 849-61.
Uptain, S. M., C. M. Kane, et al. (1997). "Basic mechanisms of transcript elongation and its regulation." Annu Rev Biochem 66: 117-72.
Vagin, A. and A. Teplyakov (1997). "MOLREP: an Automated Program for Molecular Replacement." Journal of Applied Crystallography 30(6): 1022-1025.
Vincent, J. B., M. W. Crowder, et al. (1992). "Hydrolysis of phosphate monoesters: a biological problem with multiple chemical solutions." Trends Biochem Sci 17(3): 105-10.
Wallden, K., B. Ruzzenente, et al. (2005). "Structural basis for substrate specificity of the human mitochondrial deoxyribonucleotidase." Structure 13(7): 1081-8.
Wang, W., R. Kim, et al. (2001). "Crystal structure of phosphoserine phosphatase from Methanococcus jannaschii, a hyperthermophile, at 1.8 A resolution." Structure 9(1): 65-71.
Whittaker, C. A. and R. O. Hynes (2002). "Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere." Mol Biol Cell 13(10): 3369-87.
Worku, Y. and A. C. Newby (1982). "Nucleoside exchange catalysed by the cytoplasmic 5'-nucleotidase." Biochem J 205(3): 503-10.
Zhang, G., A. S. Mazurkie, et al. (2002). "Kinetic evidence for a substrate-induced fit in phosphonoacetaldehyde hydrolase catalysis." Biochemistry 41(45): 13370-7.
Zhao, K., X. Chai, et al. (2003). "Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-acetyl ADP ribose and histone peptide." Structure 11(11): 1403-11.
Zimmermann, H. (1992). "5'-Nucleotidase: molecular structure and functional aspects." Biochem J 285 ( Pt 2): 345-65.
Adelman, K., W. Wei, et al. (2006). "Drosophila Paf1 modulates chromatin structure at actively transcribed genes." Mol Cell Biol 26(1): 250-60.
Ahn, S. H., M. Kim, et al. (2004). "Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3' end processing." Mol Cell 13(1): 67-76.
Akhtar, M. S., M. Heidemann, et al. (2009). "TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA polymerase II." Mol Cell 34(3): 387-93.
Ansari, A. and M. Hampsey (2005). "A role for the CPF 3'-end processing machinery in RNAP II-dependent gene looping." Genes Dev 19(24): 2969-78.
Arndt, K. M. and C. M. Kane (2003). "Running with RNA polymerase: eukaryotic transcript elongation." Trends Genet 19(10): 543-50.
Betz, J. L., M. Chang, et al. (2002). "Phenotypic analysis of Paf1/RNA polymerase II complex mutations reveals connections to cell cycle regulation, protein synthesis, and lipid and nucleic acid metabolism." Mol Genet Genomics 268(2): 272-85.
Carpten, J. D., C. M. Robbins, et al. (2002). "HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome." Nat Genet 32(4): 676-80.
Chang, M., D. French-Cornay, et al. (1999). "A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling." Mol Cell Biol 19(2): 1056-67.
Chaudhary, K., S. Deb, et al. (2007). "Human RNA polymerase II-associated factor complex: dysregulation in cancer." Oncogene 26(54): 7499-507.
Chen, Y., Y. Yamaguchi, et al. (2009). "DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA polymerase II elongation." Genes Dev 23(23): 2765-77.
Costa, P. J. and K. M. Arndt (2000). "Synthetic lethal interactions suggest a role for the Saccharomyces cerevisiae Rtf1 protein in transcription elongation." Genetics 156(2): 535-47.
Kanin, E. I., R. T. Kipp, et al. (2007). "Chemical inhibition of the TFIIH-associated kinase Cdk7/Kin28 does not impair global mRNA synthesis." Proc Natl Acad Sci U S A 104(14): 5812-7.
Kaplan, C. D., M. J. Holland, et al. (2005). "Interaction between transcription elongation factors and mRNA 3'-end formation at the Saccharomyces cerevisiae GAL10-GAL7 locus." J Biol Chem 280(2): 913-22.
Kim, J., M. Guermah, et al. "The human PAF1 complex acts in chromatin transcription elongation both independently and cooperatively with SII/TFIIS." Cell 140(4): 491-503.
Kim, T. and S. Buratowski (2009). "Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions." Cell 137(2): 259-72.
Kim, Y. J., S. Bjorklund, et al. (1994). "A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II." Cell 77(4): 599-608.
Kizer, K. O., H. P. Phatnani, et al. (2005). "A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation." Mol Cell Biol 25(8): 3305-16.
Koleske, A. J. and R. A. Young (1994). "An RNA polymerase II holoenzyme responsive to activators." Nature 368(6470): 466-9.
Krogan, N. J., J. Dover, et al. (2003). "The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation." Mol Cell 11(3): 721-9.
Krogan, N. J., M. Kim, et al. (2002). "RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach." Mol Cell Biol 22(20): 6979-92.
Laribee, R. N., N. J. Krogan, et al. (2005). "BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex." Curr Biol 15(16): 1487-93.
Lee, S. H., K. Baek, et al. (2008). "Large nucleotide-dependent conformational change in Rab28." FEBS Lett 582(29): 4107-11.
Li, B., M. Carey, et al. (2007). "The role of chromatin during transcription." Cell 128(4): 707-19.
Lin, L., J. H. Zhang, et al. (2008). "The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene." Proc Natl Acad Sci U S A 105(45): 17420-5.
Liu, Y., L. Warfield, et al. (2009). "Phosphorylation of the transcription elongation factor Spt5 by yeast Bur1 kinase stimulates recruitment of the PAF complex." Mol Cell Biol 29(17): 4852-63.
Meinhart, A. and P. Cramer (2004). "Recognition of RNA polymerase II carboxy-terminal domain by 3'-RNA-processing factors." Nature 430(6996): 223-6. Moniaux, N., C. Nemos, et al. (2009). "The human RNA polymerase II-associated factor 1 (hPaf1): a new regulator of cell-cycle progression." PLoS One 4(9): e7077.
Moniaux, N., C. Nemos, et al. (2006). "The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis." Oncogene 25(23): 3247-57.
Mosimann, C., G. Hausmann, et al. (2006). "Parafibromin/Hyrax activatesWnt/Wg target gene transcription by direct association with beta-catenin/Armadillo." Cell 125(2): 327-41.
Mosimann, C., G. Hausmann, et al. (2009). "The role of Parafibromin/Hyrax as a nuclear Gli/Ci-interacting protein in Hedgehog target gene control." Mech Dev 126(5-6): 394-405.
Mozdy, A. D., E. R. Podell, et al. (2008). "Multiple yeast genes, including Paf1 complex genes, affect telomere length via telomerase RNA abundance." Mol Cell Biol 28(12): 4152-61.
Mueller, C. L. and J. A. Jaehning (2002). "Ctr9, Rtf1, and Leo1 are components of the Paf1/RNA polymerase II complex." Mol Cell Biol 22(7): 1971-80.
Mueller, C. L., S. E. Porter, et al. (2004). "The Paf1 complex has functions independent of actively transcribing RNA polymerase II." Mol Cell 14(4): 447-56.
Ng, H. H., F. Robert, et al. (2003). "Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity." Mol Cell 11(3): 709-19.
Nordick, K., M. G. Hoffman, et al. (2008). "Direct interactions between the Paf1 complex and a cleavage and polyadenylation factor are revealed by dissociation of Paf1 from RNA polymerase II." Eukaryot Cell 7(7): 1158-67.
O'Sullivan, J. M., S. M. Tan-Wong, et al. (2004). "Gene loops juxtapose promoters and terminators in yeast." Nat Genet 36(9): 1014-8.
Oh, S., H. Zhang, et al. (2004). "A mechanism related to the yeast transcriptional regulator Paf1c is required for expression of the Arabidopsis FLC/MAF MADS box gene family." Plant Cell 16(11): 2940-53.
Pan, X., S. Eathiraj, et al. (2006). "TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism." Nature 442(7100): 303-6.
Pavri, R., B. Zhu, et al. (2006). "Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II." Cell 125(4): 703-17.
Penheiter, K. L., T. M. Washburn, et al. (2005). "A posttranscriptional role for the yeast Paf1-RNA polymerase II complex is revealed by identification of primary targets." Mol Cell 20(2): 213-23.
Phatnani, H. P. and A. L. Greenleaf (2006). "Phosphorylation and functions of the RNA polymerase II CTD." Genes Dev 20(21): 2922-36.
Phatnani, H. P., J. C. Jones, et al. (2004). "Expanding the functional repertoire of CTD kinase I and RNA polymerase II: novel phosphoCTD-associating proteins in the yeast proteome." Biochemistry 43(50): 15702-19.
Porter, S. E., T. M. Washburn, et al. (2002). "The yeast pafl-rNA polymerase II complex is required for full expression of a subset of cell cycle-regulated genes." Eukaryot Cell 1(5): 830-42.
Proudfoot, N. (2004). "New perspectives on connecting messenger RNA 3' end formation to transcription." Curr Opin Cell Biol 16(3): 272-8.
Qiu, H., C. Hu, et al. (2009). "Phosphorylation of the Pol II CTD by KIN28 enhances BUR1/BUR2 recruitment and Ser2 CTD phosphorylation near promoters." Mol Cell 33(6): 752-62.
Reed, S. I., J. Ferguson, et al. (1988). "Isolation and characterization of two genes encoding yeast mating pheromone signaling elements: CDC72 and CDC73." Cold Spring Harb Symp Quant Biol 53 Pt 2: 621-7.
Rondon, A. G., M. Gallardo, et al. (2004). "Molecular evidence indicating that the yeast PAF complex is required for transcription elongation." EMBO Rep 5(1): 47-53.
Rozenblatt-Rosen, O., C. M. Hughes, et al. (2005). "The parafibromin tumor suppressor protein is part of a human Paf1 complex." Mol Cell Biol 25(2): 612-20.
Rozenblatt-Rosen, O., T. Nagaike, et al. (2009). "The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors." Proc Natl Acad Sci U S A 106(3): 755-60.
Schlichting, I., S. C. Almo, et al. (1990). "Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis." Nature 345(6273): 309-15.
Sheldon, K. E., D. M. Mauger, et al. (2005). "A Requirement for the Saccharomyces cerevisiae Paf1 complex in snoRNA 3' end formation." Mol Cell 20(2): 225-36.
Shi, X., M. Chang, et al. (1997). "Cdc73p and Paf1p are found in a novel RNA polymerase II-containing complex distinct from the Srbp-containing holoenzyme." Mol Cell Biol 17(3): 1160-9.
Shi, X., A. Finkelstein, et al. (1996). "Paf1p, an RNA polymerase II-associated factor in Saccharomyces cerevisiae, may have both positive and negative roles in transcription." Mol Cell Biol 16(2): 669-76.
Shilatifard, A. (2008). "Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation." Curr Opin Cell Biol 20(3): 341-8.
Sikorski, T. W. and S. Buratowski (2009). "The basal initiation machinery: beyond the general transcription factors." Curr Opin Cell Biol 21(3): 344-51.
Simic, R., D. L. Lindstrom, et al. (2003). "Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes." EMBO J 22(8): 1846-56.
Singh, B. N. and M. Hampsey (2007). "A transcription-independent role for TFIIB in gene looping." Mol Cell 27(5): 806-16.
Squazzo, S. L., P. J. Costa, et al. (2002). "The Paf1 complex physically and functionally associates with transcription elongation factors in vivo." EMBO J 21(7): 1764-74.
Steinmetz, E. J., N. K. Conrad, et al. (2001). "RNA-binding protein Nrd1 directs poly(A)-independent 3'-end formation of RNA polymerase II transcripts." Nature 413(6853): 327-31.
Stenmark, H. and V. M. Olkkonen (2001). "The Rab GTPase family." Genome Biol 2(5): REVIEWS3007.
Strawn, L. A., C. A. Lin, et al. (2009). "Mutants of the Paf1 complex alter phenotypic expression of the yeast prion [PSI+]." Mol Biol Cell 20(8): 2229-41.
Wade, P. A., W. Werel, et al. (1996). "A novel collection of accessory factors associated with yeast RNA polymerase II." Protein Expr Purif 8(1): 85-90.
Wang, P., M. R. Bowl, et al. (2008). "Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice." Mol Cell Biol 28(9): 2930-40.
Warner, M. H., K. L. Roinick, et al. (2007). "Rtf1 is a multifunctional component of the Paf1 complex that regulates gene expression by directing cotranscriptional histone modification." Mol Cell Biol 27(17): 6103-15.
Wood, A., J. Schneider, et al. (2003). "The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p." J Biol Chem 278(37): 34739-42.
Wood, A. and A. Shilatifard (2006). "Bur1/Bur2 and the Ctk complex in yeast: the split personality of mammalian P-TEFb." Cell Cycle 5(10): 1066-8.
Woodard, G. E., L. Lin, et al. (2005). "Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression." Oncogene 24(7): 1272-6.
Wyce, A., T. Xiao, et al. (2007). "H2B ubiquitylation acts as a barrier to Ctk1 nucleosomal recruitment prior to removal by Ubp8 within a SAGA-related complex." Mol Cell 27(2): 275-88.
Yart, A., M. Gstaiger, et al. (2005). "The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II." Mol Cell Biol 25(12): 5052-60.
Zhang, Y., M. L. Sikes, et al. (2009). "The Paf1 complex is required for efficient transcription elongation by RNA polymerase I." Proc Natl Acad Sci U S A 106(7): 2153-8.
Zheng, J. Y., T. Koda, et al. (1998). "A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized to the medial Golgi cisternae." J Cell Sci 111 ( Pt 8): 1061-9.
Zhu, B., S. S. Mandal, et al. (2005). "The human PAF complex coordinates transcription with events downstream of RNA synthesis." Genes Dev 19(14): 1668-73.