Biopolym. Cell. 2012; 28(3):202-206.
http://dx.doi.org/10.7124/bc.00004E
Minireviews
The new base excision repair pathway in mammals mediated by tyrosyl-DNA-phosphodiesterase 1
1Lebedeva N. A., 1Rechkunova N. I., 1Lavrik O. I.
  1. Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
    8, Akademika Lavrentieva Ave., Novosibirsk, Russian Federation, 630090

Abstract

Human tyrosyl-DNA phosphodiesterase 1 (Tdp1) hydrolyzesthe phosphodiester bond at a DNA 3' end linked to a tyrosyl moiety and has been implicated in the repair of Topoisomerase I (TopI )-DNA covalent complexes. Tdp1 can also hydrolyze other 3' end DNA alterations including 3' phosphoglycolate and 3' abasic (AP) sites, and exhibits the 3' nucleosidase activity indicating that it may function as a general 3' end-processing DNA repair enzyme. Recently we have shown a new Tdp1 activity generating DNA strand break with the 3' phosphate termini from the AP site. AP sites are formed spontaneously and are inevitable intermediates during base excision repair of DNA base damages. AP sites are both mutagenic and cytotoxic, and key enzymes for their removal are AP endonucleases. However, AP endonuclease independent repair, initiated by DNA glycosylases performing beta, delta-elimination cleavage of the AP sites, has been described in mammalian cells. Here, we describe another AP endonuclease independent repair pathway for removal of AP sites that is initiated by tyrosyl phosphodiesterase Tdp1. We propose that repair is completed by the action of a polynucleotide kinase, a DNA polymerase and finally a DNA ligase to seal the gap
Keywords: base excision repair, AP site, tyrosyl-DNA phosphodiesterase 1
Full text: (PDF, in English)

References

[1] Yang S. W., Burgin A. B. Jr., Huizenga B. N., Robertson C. A., Yao K. C., Nash H. A. A eukaryotic enzyme that can disjoin deadend covalent complexes between DNA and type I topoisomerases Proc. Natl Acad. Sci. USA 1996 93, N 21:11534– 11539.
[2] Dexheimer T. S., Antony S., Marchand C., Pommier Y. Tyrosyl-DNA phosphodiesterase as a target for anticancer therapy Anticancer Agents Med. Chem 2008 8, N 4:381–389.
[3] Barnes D. E., Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells Annu. Rev. Genet 2004 38:445–476.
[4] Wiederhold L., Leppard J. B., Kedar P., Karimi-Busheri F., Rasouli-Nia A., Weinfeld M., Tomkinson A. E., Izumi T., Prasad R., Wilson S. H., Mitra S., Hazra T. K. AP endonuclease-independent DNA base excision repair in human cells Mol. Cell 2004 15, N 2:209–220.
[5] Interthal H., Chen H. J., Champoux J. J. Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages J. Biol. Chem 2005 280, N 43:36518–36528.
[6] Hsiang Y. H., Hertzberg R., Hecht S., Liu L. F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I J. Biol. Chem 1985 260, N 27:14873–14878.
[7] Nitiss K. C., Malik M., He X., White S. W., Nitiss J. L. TyrosylDNA phosphodiesterase (Tdp1) participates in the repair of Top2media ted DNA damage Proc. Natl Acad. Sci. USA 2006 103, N 24:8953–8958.
[8] Dexheimer T. S., Stephen A. G., Fivash M. J., Fisher R. J., Pommier Y. The DNA binding and 3'-end preferential activity of human tyrosyl-DNA phosphodiesterase Nucleic Acids Res 2010 38, N 7:2444–2452.
[9] Cortes Ledesma F., El Khamisy S. F., Zuma M. C., Osborn K., Caldecott K. W. A human 5'-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage Nature 2009 461, N 7264:674–678.
[10] El-Khamisy S. F., Saifi G. M., Weinfeld M., Johansson F., Helleday T., Lupski J. R., Caldecott K. W. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1 Nature 2005 434, N 7029:108–113.
[11] Plo I., Liao Z. Y., Barcelo J. M., Kohlhagen G., Caldecott K. W., Weinfeld M., Pommier Y. Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions DNA Repair (Amst) 2003 2, N 10 P. 1087–1100.
[12] Lebedeva N. A., Rechkunova N. I., Lavrik O. I. AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1 FEBS Lett 2011 585, N 4:683–686.
[13] Lindahl T., Wood R. D. Quality control by DNA repair Science 1999 286, N 5446:1897–1905.
[14] Mitra S., Hazra T. K., Roy R., Ikeda S., Biswas T., Lock J., Boldogh I., Izumi T. Complexities of DNA base excision repair in mammalian cells Mol. Cells 1997 7, N 3:305–312.
[15] Nash H. M., Bruner H. D., Scharer O. D., Addona T. A., Spooner E., Lane W. S., Verdine G. L. Cloning of a yeast 8-oxoguanine DNA glycosylase reveals the existence of a base-excision DNA-repair protein superfamily Curr. Biol 1996 6, N 8:968– 980.
[16] Zharkov D. O., Shoham G., Grollman A. P. Structural characterization of the Fpg family of DNA glycosylases DNA Repair (Amst.)–2003 2, N 8:839–862.
[17] Karimi-Busheri F., Daly G., Robins P., Canas B., Pappin D. J., Sgouros J., Miller G. G., Fakhrai H., Davis E. M., Le Beau M. M., Weinfeld M. Molecular characterization of a human DNA kinase J. Biol. Chem 1999 274, N 34:24187–24194.
[18] Karimi-Busheri F., Lee J., Tomkinson A. E., Weinfeld M. Repair of DNA strand gaps and nicks containing 3'-phosphate and 5'hydroxyl termini by purified mammalian enzymes Nucleic Acids Res 1998 26, N 19:4395–4400.
[19] Wilson D. M. 3rd. Processing of nonconventional DNA strand break ends Environ. Mol. Mutagen 2007 48, N 9:772–782.
[20] Chiang S. C., Carroll J., El-Khamisy S. F. TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage Cell Cycle 2010 9, N 3 P. 588–595.
[21] El-Khamisy S. F. To live or to die: a matter of processing damaged DNA termini in neurons EMBO Mol. Med 2011 3, N 2 P. 78–88.
[22] Das B. B., Dexheimer T. S., Maddali K., Pommier Y. Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria Proc. Natl Acad. Sci. USA 2010 107, N 46:19790–19795.
[23] Nilsen L., Forstrom R. J., Bjoras M., Alseth I. AP endonuclease independent repair of abasic sites in Schizosaccharomyces pombe Nucleic Acids Res 2012 40, N 5:2000–2009.
[24] Liu C., Pouliot J. J., Nash H. A. Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1 Proc. Natl Acad. Sci. USA 2002 99, N 23 P. 14970–14975.
[25] Inamdar K. V., Pouliot J. J., Zhou T., Lees-Miller S. P., RasouliNia A., Povirk L. F. Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1 J. Biol. Chem 2002 277, N 30:27162–27168.
[26] Povirk L. F. DNA damage and mutagenesis by radiomimetic DNA-cleaving agents: bleomycin, neocarzinostatin and other enediynes Mutat. Res 1996 355, N 1–2:71–89.
[27] Davies D. R., Interthal H., Champoux J. J., Hol W. G. Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide Chem. Biol 2003 10, N 2:139–147.
[28] Davies D. R., Interthal H., Champoux J. J., Hol W. G. Explorations of peptide and oligonucleotide binding sites of tyrosylDNA phosphodiesterase using vanadate complexes J. Med. Chem 2004 47, N 4:829–837.
[29] Interthal H., Champoux J. J. Effects of DNA and protein size on substrate cleavage by human tyrosyl-DNA phosphodiesterase 1 Biochem. J 2011 436, N 3:559–566.
[30] Interthal H., Pouliot J. J., Champoux J. J. The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D super family Proc. Natl Acad. Sci. USA 2001 98, N 21:12009– 12014.
[31] Davies D. R., Interthal H., Champoux J. J., Hol W. G. Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures J. Mol. Biol 2002 324, N 5:917–932.
[32] Takashima H., Boerkoel C. F., John J., Saifi G. M., Salih M. A., Armstrong D., Mao Y., Quiocho F. A., Roa B. B., Nakagawa M., Stockton D. W., Lupski J. R. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy Nat. Genet 2002 32, N 2:267–272.
[33] Interthal H., Chen H. J., Kehl-Fie T. E., Zotzmann J., Leppard J. B., Champoux J. J. SCAN1 mutant Tdp1 accumulates the enzymeDNA intermediate and causes camptothecin hypersensitivity EMBO J 2005 24, N 12:2224–2233.
[34] Hirano R., Interthal H., Huang C., Nakamura T., Deguchi K., Choi K., Bhattacharjee M. B., Arimura K., Umehara F., Izumo S., Northrop J. L., Salih M. A., Inoue K., Armstrong D. L., Champoux J. J., Takashima H., Boerkoel C. F. Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation? EMBO J 2007 26, N 22:4732–4743.
[35] Katyal S., El-Khamisy S. F., Russell H. R., Li Y., Ju L., Caldecott K. W., McKinnon P. J. TDP1 facilitates chromosomal singlestrand break repair in neurons and is neuroprotective in vivo EMBO J 2007 26, N 22:4720–4731.
[36] Miao Z. H., Agama K., Sordet O., Povirk L., Kohn K. W., Pommier Y. Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes DNA Repair (Amst) 2006 5, N 12:1489–1494.