TDP1

Tyrosyl-DNA phosphodiesterase 1 is an enzyme that in humans is encoded by the TDP1 gene.[5][6][7]

TDP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JY1, 1MU7, 1MU9, 1NOP, 1QZQ, 1RFF, 1RFI, 1RG1, 1RG2, 1RGT, 1RGU, 1RH0
Identifiers
Aliases	TDP1, tyrosyl-DNA phosphodiesterase 1
External IDs	OMIM: 607198 MGI: 1920036 HomoloGene: 5424 GeneCards: TDP1
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q32.11 Start 89,954,939 bp[1] End 90,044,768 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 E Start 99,884,517 bp[2] End 99,955,219 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphoric diester hydrolase activity • single-stranded DNA binding • nuclease activity • double-stranded DNA binding • 3'-tyrosyl-DNA phosphodiesterase activity • exonuclease activity • GO:0001948 protein binding • hydrolase activity Cellular component • cytoplasm • cell membrane • intracellular membrane-bounded organelle • cell nucleus Biological process • single strand break repair • double-strand break repair • DNA repair • nucleic acid phosphodiester bond hydrolysis • cellular response to DNA damage stimulus Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	55775	104884
Ensembl	ENSG00000042088	ENSMUSG00000021177
UniProt	Q9NUW8	Q8BJ37
RefSeq (mRNA)	NM_001008744 NM_018319 NM_001330205	NM_028354
RefSeq (protein)	NP_001008744 NP_001317134 NP_060789	n/a
Location (UCSC)	Chr 14: 89.95 – 90.04 Mb	Chr 12: 99.88 – 99.96 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of Type I topoisomerase 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.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000042088 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021177 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Davies DR, Interthal H, Champoux JJ, Hol WG (Feb 2002). "The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1". Structure. 10 (2): 237–48. doi:10.1016/S0969-2126(02)00707-4. PMID 11839309.
6. Takashima H, Boerkoel CF, John J, Saifi GM, Salih MA, Armstrong D, Mao Y, Quiocho FA, Roa BB, Nakagawa M, Stockton DW, Lupski JR (Sep 2002). "Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy". Nat Genet. 32 (2): 267–72. doi:10.1038/ng987. PMID 12244316.
7. "Entrez Gene: TDP1 tyrosyl-DNA phosphodiesterase 1".

Further reading

• El-Khamisy SF, Caldecott KW (2007). "TDP1-dependent DNA single-strand break repair and neurodegeneration". Mutagenesis. 21 (4): 219–24. doi:10.1093/mutage/gel024. PMID 16775218.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Pouliot JJ, Yao KC, Robertson CA, Nash HA (1999). "Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes" (PDF). Science. 286 (5439): 552–5. doi:10.1126/science.286.5439.552. PMID 10521354.
• Interthal H, Pouliot JJ, Champoux JJ (2001). "The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily". Proc. Natl. Acad. Sci. U.S.A. 98 (21): 12009–14. doi:10.1073/pnas.211429198. PMC 59758. PMID 11572945.
• Inamdar KV, Pouliot JJ, Zhou T, et al. (2002). "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 (30): 27162–8. doi:10.1074/jbc.M204688200. PMID 12023295.
• Davies DR, Interthal H, Champoux JJ, Hol WG (2003). "Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures". J. Mol. Biol. 324 (5): 917–32. doi:10.1016/S0022-2836(02)01154-3. PMID 12470949.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Heilig R, Eckenberg R, Petit JL, et al. (2003). "The DNA sequence and analysis of human chromosome 14". Nature. 421 (6923): 601–7. doi:10.1038/nature01348. PMID 12508121.
• Davies DR, Interthal H, Champoux JJ, Hol WG (2003). "Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide". Chem. Biol. 10 (2): 139–47. doi:10.1016/S1074-5521(03)00021-8. PMID 12618186.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Davies DR, Interthal H, Champoux JJ, Hol WG (2004). "Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes". J. Med. Chem. 47 (4): 829–37. doi:10.1021/jm030487x. PMID 14761185.
• Raymond AC, Rideout MC, Staker B, et al. (2004). "Analysis of human tyrosyl-DNA phosphodiesterase I catalytic residues". J. Mol. Biol. 338 (5): 895–906. doi:10.1016/j.jmb.2004.03.013. PMID 15111055.
• Yang M, Kirley TL (2004). "Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1 (hSCAN-1): identification of residues essential for enzyme activity and the Ca(2+)-induced conformational change". Biochemistry. 43 (28): 9185–94. doi:10.1021/bi049565o. PMID 15248776.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Barthelmes HU, Habermeyer M, Christensen MO, et al. (2005). "TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II". J. Biol. Chem. 279 (53): 55618–25. doi:10.1074/jbc.M405042200. PMID 15494395.
• Zhou T, Lee JW, Tatavarthi H, et al. (2005). "Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1)". Nucleic Acids Res. 33 (1): 289–97. doi:10.1093/nar/gki170. PMC 546157. PMID 15647511.
• El-Khamisy SF, Saifi GM, Weinfeld M, et al. (2005). "Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1". Nature. 434 (7029): 108–13. doi:10.1038/nature03314. PMID 15744309.
• Raymond AC, Staker BL, Burgin AB (2005). "Substrate specificity of tyrosyl-DNA phosphodiesterase I (Tdp1)". J. Biol. Chem. 280 (23): 22029–35. doi:10.1074/jbc.M502148200. PMID 15811850.

External links

• GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia with Axonal Neuropathy, Autosomal Recessive