Nucleic Acids Research, Vol 26, Issue 12 2955-2962, Copyright © 1998 by Oxford University Press
E Labourier, F Rossi, IE Gallouzi, E Allemand, G Divita and J Tazi
Human DNA topoisomerase I, known for its DNA-relaxing activity, is possibly
one of the kinases phosphorylating members of the SR protein family of
splicing factors, in vivo. Little is known about the mechanism of action of
this novel kinase. Using the prototypical SR protein SF2/ASF (SRp30a) as
model substrate, we demonstrate that serine residues phosphorylated by topo
I/kinase exclusively located within the most extended arginine-serine
repeats of the SF2/ASF RS domain. Unlike other kinases such as cdc2 and
SRPK1, which also phosphorylated serines at the RS domain, topo I/kinase
required several SR dipeptide repeats. These repeats possibly contribute to
a versatile structure in the RS domain thereby facilitating
phosphorylation. Furthermore, far-western, fluorescence spectroscopy and
kinase assays using the SF2/ASF mutants, demonstrated that kinase activity
and binding were tightly coupled. Since the deletion of N-terminal 174
amino acids of Topo I destroys SF2/ASF binding and kinase activity but not
ATP binding, we conclude that at least two distinct domains of Topo I are
necessary for kinase activity: one in the C-terminal region contributing to
the ATP binding site and the other one in the N-terminal region that allows
binding of SF2/ASF.
ARTICLES
Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor
Institut de Genetique Moleculaire de Montpellier (IGM), UMR 5535 CNRS, Universite Montpellier II, CNRS - BP 5051, 1919, route de Mende, F34293 Montpellier Cedex 5, France.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Malanga, A. Czubaty, A. Girstun, K. Staron, and F. R. Althaus Poly(ADP-ribose) Binds to the Splicing Factor ASF/SF2 and Regulates Its Phosphorylation by DNA Topoisomerase I J. Biol. Chem., July 18, 2008; 283(29): 19991 - 19998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Haynes and L. M. Iakoucheva Serine/arginine-rich splicing factors belong to a class of intrinsically disordered proteins Nucleic Acids Res., January 10, 2006; 34(1): 305 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Soret, N. Bakkour, S. Maire, S. Durand, L. Zekri, M. Gabut, W. Fic, G. Divita, C. Rivalle, D. Dauzonne, et al. Selective modification of alternative splicing by indole derivatives that target serine-arginine-rich protein splicing factors PNAS, June 14, 2005; 102(24): 8764 - 8769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tazi, N. Bakkour, J. Soret, L. Zekri, B. Hazra, W. Laine, B. Baldeyrou, A. Lansiaux, and C. Bailly Selective Inhibition of Topoisomerase I and Various Steps of Spliceosome Assembly by Diospyrin Derivatives Mol. Pharmacol., April 1, 2005; 67(4): 1186 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yu, E. Khan, M. A. Khaleque, J. Lee, G. Laco, G. Kohlhagen, S. Kharbanda, Y.-C. Cheng, Y. Pommier, and A. Bharti Phosphorylation of DNA Topoisomerase I by the c-Abl Tyrosine Kinase Confers Camptothecin Sensitivity J. Biol. Chem., December 10, 2004; 279(50): 51851 - 51861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Soret, M. Gabut, C. Dupon, G. Kohlhagen, J. Stevenin, Y. Pommier, and J. Tazi Altered Serine/Arginine-Rich Protein Phosphorylation and Exonic Enhancer-Dependent Splicing in Mammalian Cells Lacking Topoisomerase I Cancer Res., December 1, 2003; 63(23): 8203 - 8211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Marchand, P. Pourquier, G. S. Laco, N. Jing, and Y. Pommier Interaction of Human Nuclear Topoisomerase I with Guanosine Quartet-forming and Guanosine-rich Single-stranded DNA and RNA Oligonucleotides J. Biol. Chem., March 8, 2002; 277(11): 8906 - 8911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pilch, E. Allemand, M. Facompre, C. Bailly, J.-F. Riou, J. Soret, and J. Tazi Specific Inhibition of Serine- and Arginine-rich Splicing Factors Phosphorylation, Spliceosome Assembly, and Splicing by the Antitumor Drug NB-506 Cancer Res., September 1, 2001; 61(18): 6876 - 6884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Allemand, R. Gattoni, H.-M. Bourbon, J. Stevenin, J. F. Cáceres, J. Soret, and J. Tazi Distinctive Features of Drosophila Alternative Splicing Factor RS Domain: Implication for Specific Phosphorylation, Shuttling, and Splicing Activation Mol. Cell. Biol., February 15, 2001; 21(4): 1345 - 1359. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Balestrazzi, A. Chini, G. Bernacchia, A. Bracci, G. Luccarini, R. Cella, and D. Carbonera Carrot cells contain two top1 genes having the coding capacity for two distinct DNA topoisomerases I J. Exp. Bot., December 1, 2000; 51(353): 1979 - 1990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lacroix, H. Lienard, E. Labourier, M. Djavaheri-Mergny, J. Lacoste, H. Leffers, J. Tazi, C. Helene, and J.-L. Mergny Identification of two human nuclear proteins that recognise the cytosine-rich strand of human telomeres in vitro Nucleic Acids Res., April 1, 2000; 28(7): 1564 - 1575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. G. Ahuja, C. A. Felix, and P. D. Aplan The t(11;20)(p15;q11) Chromosomal Translocation Associated With Therapy-Related Myelodysplastic Syndrome Results in an NUP98-TOP1 Fusion Blood, November 1, 1999; 94(9): 3258 - 3261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Labourier, H.-M. Bourbon, I.-e. Gallouzi, M. Fostier, E. Allemand, and J. Tazi Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development Genes & Dev., March 15, 1999; 13(6): 740 - 753. [Abstract] [Full Text]
|
|
|
|
|
|
E. Labourier, J.-F. Riou, M. Prudhomme, C. Carrasco, C. Bailly, and J. Tazi Poisoning of Topoisomerase I by an Antitumor Indolocarbazole Drug: Stabilization of Topoisomerase I-DNA Covalent Complexes and Specific Inhibition of the Protein Kinase Activity Cancer Res., January 1, 1999; 59(1): 52 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Misteli, J. F. Caceres, J. Q. Clement, A. R. Krainer, M. F. Wilkinson, and D. L. Spector Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo J. Cell Biol., October 19, 1998; 143(2): 297 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lisby, J. R. Olesen, C. Skouboe, B. O. Krogh, T. Straub, F. Boege, S. Velmurugan, P. M. Martensen, A. H. Andersen, M. Jayaram, et al. Residues within the N-terminal Domain of Human Topoisomerase I Play a Direct Role in Relaxation* J. Biol. Chem., June 1, 2001; 276(23): 20220 - 20227. [Abstract] [Full Text] [PDF]
|
|