TDP1

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; OMA:TDP1 - orthologs
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 Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte right testis left testis testicle ventricular zone bone marrow cells gonad sperm embryo Top expressed in seminiferous tubule ventricular zone yolk sac secondary oocyte epiblast zygote embryo ganglionic eminence tail of embryo embryo More reference expression data BioGPS 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 protein binding hydrolase activity Cellular component cytoplasm plasma membrane intracellular membrane-bounded organelle 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

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

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. S2CID   22725759.
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". 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. Bibcode:2001PNAS...9812009I. 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. Bibcode:2002PNAS...9916899M. 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. Bibcode:2003Natur.421..601H. 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. Bibcode:2005Natur.434..108E. doi:10.1038/nature03314. PMID   15744309. S2CID   4423748.
• 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