ID   TOP1_YEAST              Reviewed;         769 AA.
AC   P04786; D6W261;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 2.
DT   27-MAR-2024, entry version 223.
DE   RecName: Full=DNA topoisomerase 1;
DE            EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10130};
DE   AltName: Full=DNA topoisomerase I;
DE   AltName: Full=Maintenance of killer protein 1;
GN   Name=TOP1; Synonyms=MAK1; OrderedLocusNames=YOL006C;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2989818; DOI=10.1073/pnas.82.13.4374;
RA   Thrash C., Bankier A.T., Barrell B.G., Sternglanz R.;
RT   "Cloning, characterization, and sequence of the yeast DNA topoisomerase I
RT   gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:4374-4378(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169874;
RA   Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA   Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA   Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA   Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA   Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA   Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA   Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA   Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA   Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA   Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA   Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA   Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA   Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA   Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA   Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA   Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL   Nature 387:98-102(1997).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   ACTIVE SITE TYR-727.
RX   PubMed=2542938; DOI=10.1073/pnas.86.10.3559;
RA   Lynn R.M., Bjornsti M.-A., Caron P.R., Wang J.C.;
RT   "Peptide sequencing and site-directed mutagenesis identify tyrosine-727 as
RT   the active site tyrosine of Saccharomyces cerevisiae DNA topoisomerase I.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:3559-3563(1989).
RN   [5]
RP   ACTIVE SITE TYR-727.
RX   PubMed=2547758; DOI=10.1016/s0021-9258(18)80002-3;
RA   Eng W.-K., Pandit S.D., Sternglanz R.;
RT   "Mapping of the active site tyrosine of eukaryotic DNA topoisomerase I.";
RL   J. Biol. Chem. 264:13373-13376(1989).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-15 AND SER-76, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ADR376;
RX   PubMed=17330950; DOI=10.1021/pr060559j;
RA   Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA   Elias J.E., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of alpha-factor-arrested
RT   Saccharomyces cerevisiae.";
RL   J. Proteome Res. 6:1190-1197(2007).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-15; SER-24 AND
RP   SER-76, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-15; SER-49 AND
RP   SER-76, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 141-363.
RX   PubMed=8747458; DOI=10.1016/s0969-2126(01)00269-6;
RA   Lue N., Sharma A., Mondragon A., Wang J.C.;
RT   "A 26 kDa yeast DNA topoisomerase I fragment: crystallographic structure
RT   and mechanistic implications.";
RL   Structure 3:1315-1322(1995).
CC   -!- FUNCTION: Releases the supercoiling and torsional tension of DNA
CC       introduced during the DNA replication and transcription by transiently
CC       cleaving and rejoining one strand of the DNA duplex. Introduces a
CC       single-strand break via transesterification at a target site in duplex
CC       DNA. The scissile phosphodiester is attacked by the catalytic tyrosine
CC       of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-
CC       enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free
CC       DNA strand then rotates around the intact phosphodiester bond on the
CC       opposing strand, thus removing DNA supercoils. Finally, in the
CC       religation step, the DNA 5'-OH attacks the covalent intermediate to
CC       expel the active-site tyrosine and restore the DNA phosphodiester
CC       backbone (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP-independent breakage of single-stranded DNA, followed by
CC         passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10130};
CC   -!- SUBUNIT: Monomer.
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, nucleoplasm.
CC       Note=Diffuse nuclear localization with some enrichment in nucleoli. On
CC       CPT treatment, cleared from nucleoli into nucleoplasm. Sumoylated forms
CC       found in both nucleoplasm and nucleoli (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: In yeast, topoisomerase I seems to be dispensable. This
CC       is thought to be due to the abundant presence of topoisomerase II that
CC       can substitute for the relaxing activity of topoisomerase I.
CC   -!- MISCELLANEOUS: Eukaryotic topoisomerase I and II can relax both
CC       negative and positive supercoils, whereas prokaryotic enzymes relax
CC       only negative supercoils.
CC   -!- MISCELLANEOUS: Present with 2970 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the type IB topoisomerase family. {ECO:0000305}.
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DR   EMBL; K03077; AAA35162.1; -; Genomic_DNA.
DR   EMBL; Z74748; CAA99005.1; -; Genomic_DNA.
DR   EMBL; BK006948; DAA10777.1; -; Genomic_DNA.
DR   PIR; A23161; ISBYT1.
DR   RefSeq; NP_014637.1; NM_001183260.1.
DR   PDB; 1OIS; X-ray; 1.90 A; A=141-363.
DR   PDBsum; 1OIS; -.
DR   AlphaFoldDB; P04786; -.
DR   SMR; P04786; -.
DR   BioGRID; 34398; 650.
DR   DIP; DIP-1705N; -.
DR   IntAct; P04786; 13.
DR   MINT; P04786; -.
DR   STRING; 4932.YOL006C; -.
DR   BindingDB; P04786; -.
DR   ChEMBL; CHEMBL5948; -.
DR   iPTMnet; P04786; -.
DR   MaxQB; P04786; -.
DR   PaxDb; 4932-YOL006C; -.
DR   PeptideAtlas; P04786; -.
DR   EnsemblFungi; YOL006C_mRNA; YOL006C; YOL006C.
DR   GeneID; 854156; -.
DR   KEGG; sce:YOL006C; -.
DR   AGR; SGD:S000005366; -.
DR   SGD; S000005366; TOP1.
DR   VEuPathDB; FungiDB:YOL006C; -.
DR   eggNOG; KOG0981; Eukaryota.
DR   GeneTree; ENSGT00940000167650; -.
DR   HOGENOM; CLU_009193_1_0_1; -.
DR   InParanoid; P04786; -.
DR   OMA; HRWKEVK; -.
DR   OrthoDB; 10940at2759; -.
DR   BioCyc; YEAST:G3O-33423-MONOMER; -.
DR   Reactome; R-SCE-4615885; SUMOylation of DNA replication proteins.
DR   BioGRID-ORCS; 854156; 5 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P04786; -.
DR   PRO; PR:P04786; -.
DR   Proteomes; UP000002311; Chromosome XV.
DR   RNAct; P04786; Protein.
DR   GO; GO:0005730; C:nucleolus; IPI:SGD.
DR   GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:SGD.
DR   GO; GO:0031298; C:replication fork protection complex; IDA:SGD.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; IDA:SGD.
DR   GO; GO:0006325; P:chromatin organization; IMP:SGD.
DR   GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR   GO; GO:0006260; P:DNA replication; IBA:GO_Central.
DR   GO; GO:0006271; P:DNA strand elongation involved in DNA replication; IMP:SGD.
DR   GO; GO:0006265; P:DNA topological change; IDA:SGD.
DR   GO; GO:0007076; P:mitotic chromosome condensation; IMP:SGD.
DR   GO; GO:0007097; P:nuclear migration; IMP:SGD.
DR   GO; GO:0000183; P:rDNA heterochromatin formation; IMP:SGD.
DR   GO; GO:0000019; P:regulation of mitotic recombination; IMP:SGD.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:SGD.
DR   GO; GO:0009303; P:rRNA transcription; IGI:SGD.
DR   GO; GO:0006368; P:transcription elongation by RNA polymerase II; IMP:SGD.
DR   CDD; cd00659; Topo_IB_C; 1.
DR   CDD; cd03488; Topoisomer_IB_N_htopoI_like; 1.
DR   Gene3D; 1.10.132.10; -; 1.
DR   Gene3D; 2.170.11.10; DNA Topoisomerase I, domain 2; 1.
DR   Gene3D; 1.10.10.41; Yeast DNA topoisomerase - domain 1; 1.
DR   InterPro; IPR011010; DNA_brk_join_enz.
DR   InterPro; IPR013034; DNA_topo_DNA_db_N_dom1.
DR   InterPro; IPR013030; DNA_topo_DNA_db_N_dom2.
DR   InterPro; IPR001631; TopoI.
DR   InterPro; IPR018521; TopoI_AS.
DR   InterPro; IPR025834; TopoI_C_dom.
DR   InterPro; IPR014711; TopoI_cat_a-hlx-sub_euk.
DR   InterPro; IPR014727; TopoI_cat_a/b-sub_euk.
DR   InterPro; IPR013500; TopoI_cat_euk.
DR   InterPro; IPR008336; TopoI_DNA-bd_euk.
DR   InterPro; IPR036202; TopoI_DNA-bd_euk_N_sf.
DR   InterPro; IPR013499; TopoI_euk.
DR   InterPro; IPR048045; Topoisomer_I_DNA-bd.
DR   PANTHER; PTHR10290:SF23; DNA TOPOISOMERASE 1; 1.
DR   PANTHER; PTHR10290; DNA TOPOISOMERASE I; 1.
DR   Pfam; PF14370; Topo_C_assoc; 1.
DR   Pfam; PF01028; Topoisom_I; 1.
DR   Pfam; PF02919; Topoisom_I_N; 1.
DR   PRINTS; PR00416; EUTPISMRASEI.
DR   SMART; SM00435; TOPEUc; 1.
DR   SUPFAM; SSF56349; DNA breaking-rejoining enzymes; 1.
DR   SUPFAM; SSF56741; Eukaryotic DNA topoisomerase I, N-terminal DNA-binding fragment; 1.
DR   PROSITE; PS00176; TOPO_IB_1; 1.
DR   PROSITE; PS52038; TOPO_IB_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; DNA-binding; Isomerase; Nucleus; Phosphoprotein;
KW   Reference proteome; Topoisomerase.
FT   CHAIN           1..769
FT                   /note="DNA topoisomerase 1"
FT                   /id="PRO_0000145211"
FT   DOMAIN          364..769
FT                   /note="Topo IB-type catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01382"
FT   REGION          1..132
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          357..358
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   REGION          420..425
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   REGION          512..514
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        10..26
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        29..43
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        87..132
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        727
FT                   /note="O-(3'-phospho-DNA)-tyrosine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01382,
FT                   ECO:0000255|PROSITE-ProRule:PRU10130,
FT                   ECO:0000269|PubMed:2542938, ECO:0000269|PubMed:2547758"
FT   SITE            296
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            344
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            375
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            432
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            458
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            501
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            558
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         14
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   MOD_RES         15
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   MOD_RES         24
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   MOD_RES         49
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         76
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   STRAND          168..170
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          173..175
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   HELIX           179..190
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   TURN            191..193
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   HELIX           196..198
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   HELIX           200..216
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   HELIX           229..231
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   HELIX           235..248
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   HELIX           256..271
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          272..275
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          278..283
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   TURN            300..303
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   HELIX           311..313
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          315..317
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          320..322
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          334..337
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          345..349
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   TURN            351..353
FT                   /evidence="ECO:0007829|PDB:1OIS"
FT   STRAND          356..361
FT                   /evidence="ECO:0007829|PDB:1OIS"
SQ   SEQUENCE   769 AA;  89995 MW;  1FBD5FCED044C4A2 CRC64;
     MTIADASKVN HELSSDDDDD VPLSQTLKKR KVASMNSASL QDEAEPYDSD EAISKISKKK
     TKKIKTEPVQ SSSLPSPPAK KSATSKPKKI KKEDGDVKVK TTKKEEQENE KKKREEEEEE
     DKKAKEEEEE YKWWEKENED DTIKWVTLKH NGVIFPPPYQ PLPSHIKLYY DGKPVDLPPQ
     AEEVAGFFAA LLESDHAKNP VFQKNFFNDF LQVLKESGGP LNGIEIKEFS RCDFTKMFDY
     FQLQKEQKKQ LTSQEKKQIR LEREKFEEDY KFCELDGRRE QVGNFKVEPP DLFRGRGAHP
     KTGKLKRRVN PEDIVLNLSK DAPVPPAPEG HKWGEIRHDN TVQWLAMWRE NIFNSFKYVR
     LAANSSLKGQ SDYKKFEKAR QLKSYIDAIR RDYTRNLKSK VMLERQKAVA IYLIDVFALR
     AGGEKSEDEA DTVGCCSLRY EHVTLKPPNT VIFDFLGKDS IRFYQEVEVD KQVFKNLTIF
     KRPPKQPGHQ LFDRLDPSIL NKYLQNYMPG LTAKVFRTYN ASKTMQDQLD LIPNKGSVAE
     KILKYNAANR TVAILCNHQR TVTKGHAQTV EKANNRIQEL EWQKIRCKRA ILQLDKDLLK
     KEPKYFEEID DLTKEDEATI HKRIIDREIE KYQRKFVREN DKRKFEKEEL LPESQLKEWL
     EKVDEKKQEF EKELKTGEVE LKSSWNSVEK IKAQVEKLEQ RIQTSSIQLK DKEENSQVSL
     GTSKINYIDP RLSVVFCKKY DVPIEKIFTK TLREKFKWAI ESVDENWRF
//