Homo sapiens L. (human) [HSA]

FULL NAME: DNA topoisomerase 1


DESCRIPTION:
The reaction catalyzed by topoisomerases leads to the conversion of one topological isomer of DNA to another.
Type I topoisomerases (EC 5.99.1.2) break a single DNA strand, whereas the type II enzymes break 2 strands of duplex DNA. Several lines of evidence suggest that topoisomerase I normally functions during transcription (summary by D'Arpa et al., 1988).

Type IB topoisomerase forms a protein clamp around the DNA duplex and creates a transient nick that permits removal of supercoils. Using real-time single-molecule observation, Koster et al. (2005) demonstrated that TOPIB releases supercoils by a swivel mechanism that involves friction between the rotating DNA and the enzyme cavity, i.e., the DNA does not freely rotate. Unlike a nicking enzyme, TOPIB did not release all the supercoils at once but rather in multiple steps. The number of supercoils removed per step followed an exponential distribution. The enzyme was found to be torque-sensitive, as the mean number of supercoils per step increased with the torque stored in the DNA. Koster et al. (2005) proposed a model for topoisomerization in which the torque drives the DNA rotation over a rugged periodic energy landscape in which the topoisomerase has a small but quantifiable probability to religate the DNA once per turn.

MISCELLANEOUS:
When a topoisomerase transiently breaks a DNA backbone bond, it simultaneously forms a protein-DNA link, in which a tyrosyl oxygen in the enzyme is joined to a DNA phosphorus at one end of the enzyme-severed DNA strand.
Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.


STRUCTURE SIMILARITY:
Belongs to the eukaryotic type I topoisomerase family.


CATALYTIC ACTIVITY:
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.


ENZYME REGULATION:
Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.


POST-TRANSLATIONAL MODIFICATION:
Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment.


PROTEIN TYPE(S):
endonuclease
DNA topoisomerase


RELATED PATHWAY(S):
DNA replication


Amino acids sequence

        10         20         30         40         50         60
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS NSEHKDSEKK
        70         80         90        100        110        120
HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA KIKKEKENGF SSPPQIKDEP
       130        140        150        160        170        180
EDDGYFVPPK EDIKPLKRPR DEDDADYKPK KIKTEDTKKE KKRKLEEEED GKLKKPKNKD
       190        200        210        220        230        240
KDKKVPEPDN KKKKPKKEEE QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF
       250        260        270        280        290        300
YYDGKVMKLS PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC
       310        320        330        340        350        360
DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI ANFKIEPPGL
       370        380        390        400        410        420
FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK WKEVRHDNKV TWLVSWTENI
       430        440        450        460        470        480
QGSIKYIMLN PSSRIKGEKD WQKYETARRL KKCVDKIRNQ YREDWKSKEM KVRQRAVALY
       490        500        510        520        530        540
FIDKLALRAG NEKEEGETAD TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK
       550        560        570        580        590        600
VPVEKRVFKN LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ
       610        620        630        640        650        660
QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK IDAKKEQLAD
       670        680        690        700        710        720
ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK LEVQATDREE NKQIALGTSK
       730        740        750        760
LNYLDPRITV AWCKKWGVPI EKIYNKTQRE KFAWAIDMAD EDYEF 

Encoded by TOP1 gene

FULL NAME: topoisomerase (DNA) I


OTHER NAME(S):
TOPI


DESCRIPTION:
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgagtgggg accacctcca caacgattcc cagatcgaag cggatttccg attgaatgat
        70         80         90        100        110        120
tctcataaac acaaagataa acacaaagat cgagaacacc ggcacaaaga acacaagaag
       130        140        150        160        170        180
gagaaggacc gggaaaagtc caagcatagc aacagtgaac ataaagattc tgaaaagaaa
       190        200        210        220        230        240
cacaaagaga aggagaagac caaacacaaa gatggaagct cagaaaagca taaagacaaa
       250        260        270        280        290        300
cataaagaca gagacaagga aaaacgaaaa gaggaaaagg ttcgagcctc tggggatgca
       310        320        330        340        350        360
aaaataaaga aggagaagga aaatggcttc tctagtccac cacaaattaa agatgaacct
       370        380        390        400        410        420
gaagatgatg gctattttgt tcctcctaaa gaggatataa agccattaaa gagacctcga
       430        440        450        460        470        480
gatgaggatg atgctgatta taaacctaag aaaattaaaa cagaagatac caagaaggag
       490        500        510        520        530        540
aagaaaagaa aactagaaga agaagaggat ggtaaattga aaaaacccaa gaataaagat
       550        560        570        580        590        600
aaagataaaa aagttcctga gccagataac aagaaaaaga agccgaagaa agaagaggaa
       610        620        630        640        650        660
cagaagtgga aatggtggga agaagagcgc tatcctgaag gcatcaagtg gaaattccta
       670        680        690        700        710        720
gaacataaag gtccagtatt tgccccacca tatgagcctc ttccagagaa tgtcaagttt
       730        740        750        760        770        780
tattatgatg gtaaagtcat gaagctgagc cccaaagcag aggaagtagc tacgttcttt
       790        800        810        820        830        840
gcaaaaatgc tcgaccatga atatactacc aaggaaatat ttaggaaaaa tttctttaaa
       850        860        870        880        890        900
gactggagaa aggaaatgac taatgaagag aagaatatta tcaccaacct aagcaaatgt
       910        920        930        940        950        960
gattttaccc agatgagcca gtatttcaaa gcccagacgg aagctcggaa acagatgagc
       970        980        990       1000       1010       1020
aaggaagaga aactgaaaat caaagaggag aatgaaaaat tactgaaaga atatggattc
      1030       1040       1050       1060       1070       1080
tgtattatgg ataaccacaa agagaggatt gctaacttca agatagagcc tcctggactt
      1090       1100       1110       1120       1130       1140
ttccgtggcc gcggcaacca ccccaagatg ggcatgctga agagacgaat catgcccgag
      1150       1160       1170       1180       1190       1200
gatataatca tcaactgtag caaagatgcc aaggttcctt ctcctcctcc aggacataag
      1210       1220       1230       1240       1250       1260
tggaaagaag tccggcatga taacaaggtt acttggctgg tttcctggac agagaacatc
      1270       1280       1290       1300       1310       1320
caaggttcca ttaaatacat catgcttaac cctagttcac gaatcaaggg tgagaaggac
      1330       1340       1350       1360       1370       1380
tggcagaaat acgagactgc tcggcggctg aaaaaatgtg tggacaagat ccggaaccag
      1390       1400       1410       1420       1430       1440
tatcgagaag actggaagtc caaagagatg aaagtccggc agagagctgt agccctgtac
      1450       1460       1470       1480       1490       1500
ttcatcgaca agcttgctct gagagcaggc aatgaaaagg aggaaggaga aacagcggac
      1510       1520       1530       1540       1550       1560
actgtgggct gctgctcact tcgtgtggag cacatcaatc tacacccaga gttggatggt
      1570       1580       1590       1600       1610       1620
caggaatatg tggtagagtt tgacttcctc gggaaggact ccatcagata ctataacaag
      1630       1640       1650       1660       1670       1680
gtccctgttg agaaacgagt ttttaagaac ctacaactat ttatggagaa caagcagccc
      1690       1700       1710       1720       1730       1740
gaggatgatc tttttgatag actcaatact ggtattctga ataagcatct tcaggatctc
      1750       1760       1770       1780       1790       1800
atggagggct tgacagccaa ggtattccgt acatacaatg cctccatcac gctacagcag
      1810       1820       1830       1840       1850       1860
cagctaaaag aactgacagc cccggatgag aacatcccag cgaagatcct ttcttataac
      1870       1880       1890       1900       1910       1920
cgtgccaatc gagctgttgc aattctttgt aaccatcaga gggcaccacc aaaaactttt
      1930       1940       1950       1960       1970       1980
gagaagtcta tgatgaactt gcaaactaag attgatgcca agaaggaaca gctagcagat
      1990       2000       2010       2020       2030       2040
gcccggagag acctgaaaag tgctaaggct gatgccaagg tcatgaagga tgcaaagacg
      2050       2060       2070       2080       2090       2100
aagaaggtag tagagtcaaa gaagaaggct gttcagagac tggaggaaca gttgatgaag
      2110       2120       2130       2140       2150       2160
ctggaagttc aagccacaga ccgagaggaa aataaacaga ttgccctggg aacctccaaa
      2170       2180       2190       2200       2210       2220
ctcaattatc tggaccctag gatcacagtg gcttggtgca agaagtgggg tgtcccaatt
      2230       2240       2250       2260       2270       2280
gagaagattt acaacaaaac ccagcgggag aagtttgcct gggccattga catggctgat
      2290
gaagactatg agttttag    

Last modification date: Oct. 2, 2011