Tyrosyl DNA Phosphodiesterase 1 (TDP1)

SCAN1; Tyr-DNA phosphodiesterase 1

SPN	U072
HGNC	18884
MGI	1920036
PubMed	20009512
RGD	1309618
UniProt	Q9NUW8
Wiki	TDP1

Tyrosyl-DNA phosphodiesterase 1 is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same isoform.

Reference

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and analysis of human chromosome 14."
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes."
Science 286:552-555(1999) [PubMed] [Europe PMC] [Abstract]

"The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily."
Proc. Natl. Acad. Sci. U.S.A. 98:12009-12014(2001) [PubMed] [Europe PMC] [Abstract]

"Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1."
J. Biol. Chem. 277:27162-27168(2002) [PubMed] [Europe PMC] [Abstract]

"Analysis of human tyrosyl-DNA phosphodiesterase I catalytic residues."
J. Mol. Biol. 338:895-906(2004) [PubMed] [Europe PMC] [Abstract]

"Substrate specificity of tyrosyl-DNA phosphodiesterase I (Tdp1)."
J. Biol. Chem. 280:22029-22035(2005) [PubMed] [Europe PMC] [Abstract]

"Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages."
J. Biol. Chem. 280:36518-36528(2005) [PubMed] [Europe PMC] [Abstract]

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Biochemical characterization of human Tyrosyl DNA Phosphodiesterase 2 (TDP2/TTRAP): a Mg2+/Mn2+-dependent phosphodiesterase specific for the repair of topoisomerase cleavage complexes."
J. Biol. Chem. 287:30842-30852(2012) [PubMed] [Europe PMC] [Abstract]

"Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures."
J. Mol. Biol. 324:917-932(2002) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1."
Structure 10:237-248(2002) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of a transition state mimic for TDP1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide."
Chem. Biol. 10:139-147(2003) [PubMed] [Europe PMC] [Abstract]

"Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes."
J. Med. Chem. 47:829-837(2004) [PubMed] [Europe PMC] [Abstract]

"Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy."
Nat. Genet. 32:267-272(2002) [PubMed] [Europe PMC] [Abstract]

"Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1)."
Nucleic Acids Res. 33:289-297(2005) [PubMed] [Europe PMC] [Abstract]

"SCAN1 mutant Tdp1 accumulates the enzyme-DNA intermediate and causes camptothecin hypersensitivity."
EMBO J. 24:2224-2233(2005) [PubMed] [Europe PMC] [Abstract]

"Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?"
EMBO J. 26:4732-4743(2007) [PubMed] [Europe PMC] [Abstract]