Homo sapiens L. (human) [HSA]

FULL NAME: Tyrosyl-DNA phosphodiesterase 1


DESCRIPTION:
DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate.
APE-independent base excision repair (BER) pathway plays an important role in the regulation of DNA repair mechanisms. In this study it has been found that recently discovered tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the AP site cleavage reaction to generate breaks with the 3'- and 5'-phosphate termini. The removal of the 3'-phosphate is performed by polynucleotide kinase phosphatase (PNKP). Tdp1 is known to interact stably with BER proteins: DNA polymerase beta (Pol β), XRCC1, PARP1 and DNA ligase III. The data suggest a role of Tdp1 in the new APE-independent BER pathway in mammals.

STRUCTURE SIMILARITY:
Belongs to the tyrosyl-DNA phosphodiesterase family.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylated on serine and/or threonine residues, but not on tyrosine residues.


PROTEIN TYPE(S):
DNase
3'-5' exonuclease


RELATED PATHWAY(S):
base excision repair (BER)


RELATED DISEASE(S):
spinocerebellar ataxia with axonal neuropathy (SCAN1)


RELATED DAMAGE:
3'-TOP1 termini
AP-site


Amino acids sequence

        10         20         30         40         50         60
MSQEGDYGRW TISSSDESEE EKPKPDKPST SSLLCARQGA ANEPRYTCSE AQKAAHKRKI
        70         80         90        100        110        120
SPVKFSNTDS VLPPKRQKSG SQEDLGWCLS SSDDELQPEM PQKQAEKVVI KKEKDISAPN
       130        140        150        160        170        180
DGTAQRTENH GAPACHRLKE EEDEYETSGE GQDIWDMLDK GNPFQFYLTR VSGVKPKYNS
       190        200        210        220        230        240
GALHIKDILS PLFGTLVSSA QFNYCFDVDW LVKQYPPEFR KKPILLVHGD KREAKAHLHA
       250        260        270        280        290        300
QAKPYENISL CQAKLDIAFG THHTKMMLLL YEEGLRVVIH TSNLIHADWH QKTQGIWLSP
       310        320        330        340        350        360
LYPRIADGTH KSGESPTHFK ADLISYLMAY NAPSLKEWID VIHKHDLSET NVYLIGSTPG
       370        380        390        400        410        420
RFQGSQKDNW GHFRLKKLLK DHASSMPNAE SWPVVGQFSS VGSLGADESK WLCSEFKESM
       430        440        450        460        470        480
LTLGKESKTP GKSSVPLYLI YPSVENVRTS LEGYPAGGSL PYSIQTAEKQ NWLHSYFHKW
       490        500        510        520        530        540
SAETSGRSNA MPHIKTYMRP SPDFSKIAWF LVTSANLSKA AWGALEKNGT QLMIRSYELG
       550        560        570        580        590        600
VLFLPSAFGL DSFKVKQKFF AGSQEPMATF PVPYDLPPEL YGSKDRPWIW NIPYVKAPDT

HGNMWVPS     

Encoded by TDP1 gene

FULL NAME: tyrosyl-DNA phosphodiesterase 1


OTHER NAME(S):
FLJ11090
MGC104252


DESCRIPTION:
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 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. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgtctcagg aaggcgatta tgggaggtgg accatatcta gtagtgatga aagtgaggaa
        70         80         90        100        110        120
gaaaagccaa aaccagacaa gccatctacc tcttctcttc tctgtgccag gcaaggagca
       130        140        150        160        170        180
gcaaatgagc ccaggtacac ctgttccgag gcccagaaag ctgcacacaa gaggaaaata
       190        200        210        220        230        240
tcacctgtga aattcagcaa tacagattca gttttacctc ccaaaaggca gaaaagcggt
       250        260        270        280        290        300
tcccaggagg acctcggctg gtgtctgtcc agcagtgatg atgagctgca accagaaatg
       310        320        330        340        350        360
ccgcagaagc aggctgagaa agtggtgatc aaaaaggaga aagacatctc tgctcccaat
       370        380        390        400        410        420
gacggcactg cccaaagaac tgaaaatcat ggcgctcccg cctgccacag gctcaaagag
       430        440        450        460        470        480
gaggaagacg agtatgagac atcaggggag ggccaggaca tttgggacat gctggataaa
       490        500        510        520        530        540
gggaacccct tccagtttta cctcactaga gtctctggag ttaagccaaa gtataactct
       550        560        570        580        590        600
ggagccctcc acatcaagga tattttatct cctttatttg ggacgcttgt ttcttcagct
       610        620        630        640        650        660
cagtttaact actgctttga cgtggactgg ctcgtaaaac agtatccacc agagttcagg
       670        680        690        700        710        720
aagaagccaa tcctgcttgt gcatggtgat aagcgagagg ctaaggctca cctccatgcc
       730        740        750        760        770        780
caggccaagc cttacgagaa catctctctc tgccaggcaa agttggatat tgcgtttgga
       790        800        810        820        830        840
acacaccaca cgaaaatgat gctgctgctc tatgaagaag gcctccgggt tgtcatacac
       850        860        870        880        890        900
acctccaacc tcatccatgc tgactggcac cagaaaactc aaggaatatg gttgagcccc
       910        920        930        940        950        960
ttatacccac gaattgctga tggaacccac aaatctggag agtcgccaac acattttaaa
       970        980        990       1000       1010       1020
gctgatctca tcagttactt gatggcttat aatgcccctt ctctcaagga gtggatagat
      1030       1040       1050       1060       1070       1080
gtcattcaca agcacgatct ctctgaaaca aatgtttatc ttattggttc aaccccagga
      1090       1100       1110       1120       1130       1140
cgctttcaag gaagtcaaaa agataattgg ggacatttta gacttaagaa gcttctgaaa
      1150       1160       1170       1180       1190       1200
gaccatgcct catccatgcc taacgcagag tcctggcctg tcgtaggtca gttttcaagc
      1210       1220       1230       1240       1250       1260
gttggctcct tgggagccga tgaatcaaag tggttatgtt ctgagtttaa agagagcatg
      1270       1280       1290       1300       1310       1320
ctgacactgg ggaaggaaag caagactcca ggaaaaagct ctgttcctct ttacttgatc
      1330       1340       1350       1360       1370       1380
tatccttctg tggaaaatgt gcggaccagt ttagaaggat atcctgctgg gggctctctt
      1390       1400       1410       1420       1430       1440
ccctatagca tccagacagc tgaaaaacag aattggctgc attcctattt tcacaaatgg
      1450       1460       1470       1480       1490       1500
tcagctgaga cttctggccg cagcaatgcc atgccacata ttaagacata tatgaggcct
      1510       1520       1530       1540       1550       1560
tctccagact tcagtaaaat tgcttggttc cttgtcacaa gcgcaaatct gtccaaggct
      1570       1580       1590       1600       1610       1620
gcctggggag cattggagaa gaatggcacc cagctgatga tccgctccta cgagctcggg
      1630       1640       1650       1660       1670       1680
gtccttttcc tcccttcagc atttggtcta gacagtttca aagtgaaaca gaagttcttc
      1690       1700       1710       1720       1730       1740
gctggcagcc aggagccaat ggccaccttt cctgtgccat atgatttgcc tccagaactg
      1750       1760       1770       1780       1790       1800
tatggaagta aagatcggcc atggatatgg aacattcctt atgtcaaagc accggatacg
      1810       1820
catgggaaca tgtgggtgcc ctcctga   

Last modification date: Oct. 10, 2011