369:
346:
2967:
2922:
2937:
2952:
2832:
243:
268:
2847:
2757:
2907:
2892:
2817:
2877:
2802:
375:
274:
40:
2862:
2772:
2787:
1379:, which inhibit TOP1, are among the most effective FDA-approved anticancer chemotherapeutic agents used in clinical practice. Higher expression of TOP1 in KRAS mutant non-small cell lung cancer and correlation to survival suggests that TOP1 inhibitors might have increased benefit when administered to treat patients with a KRAS mutant tumor.
1243:
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 lets the broken strand rotate around the intact strand, thus altering the topology of
1260:
were found to nick the DNA with a preference for a sequence of nucleotides that extends from positions -4 to -1 from the nick. The preferred nucleotides in the strand to be cut are 5'-(A/T)(G/C)(A/T)T-3' with the enzyme covalently attached to the -1 T residue, though sometimes a C residue is found
1524:
is a metastasis-suppressor gene in prostate cancer, and appears to have a role in DNA repair. Screening of 3360 compounds revealed that irinotecan-mediated TOP1 deficiency (and one other compound, cetrimonium bromide) exhibit synthetic lethality with NDRG1 deficiency in prostate cancer cells.
66:
1358:
act by trapping a subset of TOP1-DNA cleavage complexes, those with a guanine +1 in the DNA sequence. One irinotecan or SN-38 molecule stacks against the base pairs flanking the topoisomerase-induced cleavage site and poisons (inactivates) the TOP1 enzyme. The article
1252:
As reviewed by
Champoux, the type IB topoisomerases, including TOP1, form a covalent intermediate in which the active site tyrosine becomes attached to the 3' phosphate end of the cleaved strand rather than the 5' phosphate end.
2966:
2921:
1510:
and in a mouse model caused increased sensitivity to inactivation by irinotecan compared to cells with high expression of ATM. This indicates synthetic lethality of ATM deficiency with irinotecan-mediated TOP1 deficiency.
2936:
2951:
2831:
2846:
2331:
Andersen FF, Tange TØ, Sinnathamby T, Olesen JR, Andersen KE, Westergaard O, Kjems J, Knudsen BR (Sep 2002). "The RNA splicing factor ASF/SF2 inhibits human topoisomerase I mediated DNA relaxation".
1312:
of the DNA is relaxed by controlled rotation of DNA about the intact strand. Then the 5' hydroxyl end of the broken DNA strand can reverse the phosphotyrosyl bond, enabling the release of TOP1 and
1390:
arises when a combination of deficiencies in the expression of two or more genes leads to cell death, whereas a deficiency in only one of these genes does not. The deficiencies can arise through
1330:
The briefly attached, covalently bonded TOP1-DNA structure at the 3' end of a cleaved DNA single strand is called a TOP1-DNA cleavage complex, or TOP1cc. The TOP1cc is a specific target of TOP1
2255:
Subramanian, D.; Rosenstein, B. S.; Muller, M. T. (1998). "Ultraviolet-induced DNA damage stimulates topoisomerase I-DNA complex formation in vivo: Possible relationship with DNA repair".
2048:
Pavelitz T, Renfro L, Foster NR, Caracol A, Welsch P, Lao VV, Grady WB, Niedzwiecki D, Saltz LB, Bertagnolli MM, Goldberg RM, Rabinovitch PS, Emond M, Monnat RJ, Maizels N (2014).
2756:
1286:
within the N-terminal domain. The N-terminal domain is followed by a highly conserved, 421 amino acid core domain containing all of the catalytic residues except the active site
2906:
2891:
2050:"MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial"
1986:
Agrelo R, Cheng WH, Setien F, Ropero S, Espada J, Fraga MF, Herranz M, Paz MF, Sanchez-Cespedes M, Artiga MJ, Guerrero D, Castells A, von Kobbe C, Bohr VA, Esteller M (2006).
2284:"Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor"
1461:
of 5-fluorouracil/leucovorin (FU/LV) or else with irinotecan+FU/LV and were followed up for 8 years. Eleven percent of the tumors were deficient for DNA repair enzyme
382:
281:
2816:
1514:
Another pre-clinical effort was a screening study to find a compound that would be synthetically lethal with a deficiency of N-myc downstream regulated gene 1 (
954:
935:
204:
1401:
Irinotecan inactivation of TOP1 appears to be synthetically lethal in combination with deficiencies in expression of some specific DNA repair genes.
2112:"ATM expression predicts Veliparib and Irinotecan sensitivity in gastric cancer by mediating P53 independent regulation of cell cycle and apoptosis"
2876:
2801:
1405:
2995:
2736:
1690:
1672:
2156:"Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells"
1454:. A recent study was carried out with 1,264 patients with stage III colon cancer. The patients were treated with a postoperative weekly
2975:: Human DNA topoisomerase I (70 kDa) in complex with the indenoisoquinoline AI-III-52 and covalent complex with a 22 base pair DNA duplex
2930:: Human DNA Topoisomerase I (70 Kda) In Complex With The Indenoisoquinoline MJ-II-38 and Covalent Complex With A 22 Base Pair DNA Duplex
368:
1161:
1154:
1290:. This is followed by a poorly conserved linker domain of 77 amino acids. Finally there is a 53 amino acid C-terminal domain. The
1429:
gene promoters, so that WRN protein expression was high. Irinotecan was more strongly beneficial for patients with hypermethylated
2945:: Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex
345:
2154:
Wissing MD, Mendonca J, Kim E, Kim E, Shim JS, Kaelber NS, Kant H, Hammers H, Commes T, Van Diest PJ, Liu JO, Kachhap SK (2013).
1764:
2960:: Human DNA Topoisomerase I (70 Kda) In Complex With The Poison Camptothecin and Covalent Complex With A 22 Base Pair DNA Duplex
1283:
2371:"Characterization of BTBD1 and BTBD2, two similar BTB-domain-containing Kelch-like proteins that interact with Topoisomerase I"
1659:
1638:
1477:(though the effect was small), indicating some degree of synthetic lethality between irinotecan-induced TOP1 inactivation and
2840:: HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX
267:
242:
2861:
1655:
63:
2771:
1279:
1634:
1313:
184:
2855:: Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion
1554:
1503:
1493:
1485:
1375:
Since 1985, TOP1 has been known as a target for the treatment of human cancers. Camptothecin analogues irinotecan and
1308:
that attacks the DNA phosphodiester backbone. After the TOP1 covalently attaches to the 3' end of the broken strand,
2512:"The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53"
2786:
381:
280:
1542:
2205:"mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice"
2729:
1926:"KRAS driven expression signature has prognostic power superior to mutation status in non-small cell lung cancer"
1499:
374:
273:
999:
192:
1364:
1331:
1325:
980:
1875:
Liu YQ, Li WQ, Morris-Natschke SL, Qian K, Yang L, Zhu GX, Wu XB, Chen AL, Zhang SY, Nan X, Lee KH (2015).
1924:
Nagy, Ádám; Pongor, Lőrinc Sándor; Szabó, András; Santarpia, Mariacarmela; Győrffy, Balázs (2017-02-15).
1448:
Irinotecan inactivation of TOP1 may be synthetically lethal with deficient expression of DNA repair gene
2634:"SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage"
256:
1815:"A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity"
1244:
DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22.
2722:
2645:
2582:
2523:
2061:
1999:
1826:
1606:
1404:
Irinotecan inactivation of TOP1 was synthetically lethal with deficient expression of the DNA repair
1257:
171:
1537:
irradiation specifically stimulates the formation of covalent complexes between topoisomerase I and
1316:
of the DNA. The nicking and closing reactions are fast, and about 100 cycles can occur per second.
1418:
1387:
1301:
1489:
1395:
216:
1137:
1116:
1090:
1069:
1473:-deficient patients having better long-term disease free survival than patients with wild-type
2694:
2673:
2610:
2571:"Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 status"
2551:
2492:
2451:
2402:
2348:
2313:
2264:
2234:
2185:
2133:
2089:
2027:
1963:
1945:
1906:
1854:
1795:
1746:
1442:
1347:
1228:
164:
56:
2765:: HUMAN RECONSTITUTED DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX
2663:
2653:
2600:
2590:
2541:
2531:
2482:
2441:
2433:
2392:
2382:
2340:
2303:
2295:
2224:
2216:
2175:
2167:
2123:
2079:
2069:
2017:
2007:
1953:
1937:
1896:
1888:
1844:
1834:
1787:
1736:
1728:
1458:
1455:
461:
392:
336:
291:
1411:
1410:
gene in patients with colon cancer. In a 2006 study, 45 patients had colonic tumors with
436:
212:
2915:: Structural Mechanisms of Camptothecin Resistance by Mutations in Human Topoisomerase I
2900:: Structural Mechanisms of Camptothecin Resistance by Mutations in Human Topoisomerase I
2649:
2586:
2527:
2065:
2003:
1830:
2229:
2204:
2180:
2155:
2084:
2049:
2022:
1987:
1958:
1925:
1901:
1876:
1849:
1814:
1741:
1716:
1506:). A 2016 study showed that low expression of the ATM protein in gastric cancer cells
2605:
2570:
2446:
2422:"Interaction between the N-terminus of human topoisomerase I and SV40 large T antigen"
2421:
2344:
2308:
2283:
1231:, an enzyme that catalyzes the transient breaking and rejoining of a single strand of
869:
864:
859:
854:
849:
844:
839:
834:
829:
824:
819:
814:
809:
793:
788:
783:
778:
773:
768:
763:
758:
753:
748:
743:
738:
722:
717:
712:
707:
702:
697:
692:
687:
682:
677:
672:
667:
662:
657:
652:
39:
2989:
2703:
2668:
2633:
2546:
2511:
2397:
2370:
2110:
Subhash VV, Tan SH, Yeo MS, Yan FL, Peethala PC, Liem N, Krishnan V, Yong WP (2016).
1988:"Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer"
1791:
1611:
1309:
1269:
639:
1360:
1339:
454:
233:
2128:
2111:
196:
2074:
1469:
gene. The addition of irinotecan to FU/LV in the treatment protocol resulted in
220:
2369:
Xu L, Yang L, Hashimoto K, Anderson M, Kohlhagen G, Pommier Y, D'Arpa P (2002).
1695:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1677:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1534:
1305:
1291:
2638:
Proceedings of the
National Academy of Sciences of the United States of America
2575:
Proceedings of the
National Academy of Sciences of the United States of America
2516:
Proceedings of the
National Academy of Sciences of the United States of America
1300:
As further summarized by
Pommier and by Seol et al., TOP1 breaks the DNA by a
537:
17:
2825:: HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX
1778:
Champoux JJ (2001). "DNA topoisomerases: structure, function, and mechanism".
1492:
DNA repair deficiencies common in cancers. For instance, the DNA repair gene
1335:
1265:
353:
250:
200:
2536:
2299:
1949:
2629:
2437:
2282:
Labourier E, Rossi F, Gallouzi IE, Allemand E, Divita G, Tazi J (Jun 1998).
2012:
1839:
1580:
1376:
899:
597:
475:
420:
407:
319:
306:
208:
2677:
2658:
2614:
2595:
2555:
2487:
2470:
2406:
2352:
2238:
2189:
2137:
2093:
2031:
1967:
1910:
1858:
1799:
1750:
1488:
studies indicating synthetic lethality of irinotecan with other genetic or
2496:
2455:
2387:
2317:
2268:
1201:
1196:
1391:
1294:
1287:
1274:
1185:
1044:
1025:
2708:
2698:
2220:
1562:
1465:
due to a deletion of a string of thymidines in the DNA sequence of the
1011:
966:
2171:
1941:
1892:
1732:
1264:
The TOP1 protein of humans has been subdivided into four regions. The
789:
DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex
653:
DNA topoisomerase type I (single strand cut, ATP-independent) activity
141:
137:
133:
129:
125:
121:
117:
113:
109:
105:
101:
97:
93:
89:
85:
2471:"Identification of a nucleolin binding site in human topoisomerase I"
1462:
1450:
1217:
1169:
921:
723:
RNA polymerase II cis-regulatory region sequence-specific DNA binding
1592:
1574:
1568:
1516:
1433:
promoters (39.4 months survival) than for those with unmethylated
1355:
1351:
884:
880:
1224:
188:
2718:
1545:, a process that removes UVB-induced, and other, DNA damages.
1338:. Irinotecan is an analogue of the cytotoxic natural alkaloid
2714:
1877:"Perspectives on biologically active camptothecin derivatives"
1586:
1538:
1232:
2693:
Overview of all the structural information available in the
2885:: Human topoisomerase I (Topo70) double mutant K532R/Y723F
1425:
expression), and 43 patients had tumors with unmethylated
2203:
Dominick G, Bowman J, Li X, Miller RA, Garcia GG (2016).
2810:: CRYSTAL STRUCTURE OF HUMAN TOPOISOMERASE I DNA COMPLEX
444:
1334:. One of the first inhibitors shown to target TOP1 is
2420:
Haluska P, Saleem A, Edwards TK, Rubin EH (Apr 1998).
1363:
lists other analogues of camptothecin and the article
1541:. Topoisomerase I appears to have a direct role in
609:
2469:Bharti AK, Olson MO, Kufe DW, Rubin EH (Jan 1996).
1130:
1109:
1083:
1062:
2250:
2248:
1651:
1649:
1647:
1630:
1628:
1626:
1346:. Irinotecan is especially effective through its
1268:214 amino acids are dispensable for relaxation of
175:, TOPI, topoisomerase (DNA) I, DNA topoisomerase I
1717:"Drugging topoisomerases: lessons and challenges"
1441:gene promoter is hypermethylated in about 38% of
391:
290:
2510:Gobert C, Skladanowski A, Larsen AK (Aug 1999).
2364:
2362:
1304:reaction using the active site tyrosine as the
1813:Seol Y, Zhang H, Pommier Y, Neuman KC (2012).
1656:GRCm38: Ensembl release 89: ENSMUSG00000070544
2730:
8:
2043:
2041:
1635:GRCh38: Ensembl release 89: ENSG00000198900
1297:723 is found within the C-terminal domain.
673:core promoter sequence-specific DNA binding
2737:
2723:
2715:
2149:
2147:
2105:
2103:
1367:lists other compounds which inhibit TOP1.
895:
635:
432:
331:
228:
74:
2667:
2657:
2604:
2594:
2545:
2535:
2486:
2445:
2396:
2386:
2307:
2228:
2179:
2127:
2083:
2073:
2021:
2011:
1981:
1979:
1977:
1957:
1900:
1848:
1838:
1765:"Entrez Gene: TOP1 topoisomerase (DNA) I"
1740:
1710:
1708:
1706:
1704:
1398:or by inhibition of a gene's expression.
1284:interaction with other cellular proteins
703:protein serine/threonine kinase activity
2752:
1622:
1437:promoters (20.7 months survival). The
845:circadian regulation of gene expression
2569:Mao Y, Mehl IR, Muller MT (Feb 2002).
29:
2870:: Human Topoisomerase I Ara-C Complex
1870:
1868:
396:
357:
352:
295:
254:
249:
7:
2780:: HUMAN TOPOISOMERASE I/DNA COMPLEX
2475:The Journal of Biological Chemistry
754:replication fork protection complex
1504:hypermethylation of ATM in cancers
1127:
1106:
1080:
1059:
1035:
1016:
990:
971:
945:
926:
614:
532:
470:
449:
25:
1342:, obtained from the Chinese tree
1220:that in humans is encoded by the
2965:
2950:
2935:
2920:
2905:
2890:
2875:
2860:
2845:
2830:
2815:
2800:
2785:
2770:
2755:
1792:10.1146/annurev.biochem.70.1.369
1533:Exposure of human HeLA cells to
1502:(silenced) in many cancers (see
380:
373:
367:
344:
279:
272:
266:
241:
38:
1930:International Journal of Cancer
870:peptidyl-serine phosphorylation
713:protein domain specific binding
598:More reference expression data
1:
2795:: TOPOISOMERASE I/DNA COMPLEX
2707:(DNA topoisomerase 1) at the
2345:10.1016/s0022-2836(02)00815-x
2129:10.1158/1535-7163.MCT-15-1002
365:
264:
2996:Genes on human chromosome 20
2333:Journal of Molecular Biology
2075:10.1371/journal.pone.0108483
1992:Proc. Natl. Acad. Sci. U.S.A
1819:Proc. Natl. Acad. Sci. U.S.A
1280:nuclear localization signals
698:single-stranded DNA binding
693:double-stranded DNA binding
3012:
1543:nucleotide excision repair
1323:
668:DNA topoisomerase activity
518:superior surface of tongue
2750:
1691:"Mouse PubMed Reference:"
1673:"Human PubMed Reference:"
1200:
1195:
1191:
1184:
1168:
1162:Chr 2: 160.49 – 160.56 Mb
1149:
1134:
1113:
1102:
1087:
1066:
1055:
1042:
1038:
1023:
1019:
1010:
997:
993:
978:
974:
965:
952:
948:
933:
929:
920:
905:
898:
894:
878:
638:
634:
622:
617:
608:
595:
544:
535:
482:
473:
443:
435:
431:
414:
401:
364:
343:
334:
330:
313:
300:
263:
240:
231:
227:
182:
179:
169:
162:
157:
82:
77:
60:
55:
50:
46:
37:
32:
2628:Mao Y, Sun M, Desai SD,
2537:10.1073/pnas.96.18.10355
1155:Chr 20: 41.03 – 41.12 Mb
27:DNA topoisomerase enzyme
2013:10.1073/pnas.0600645103
1840:10.1073/pnas.1206480109
1553:TOP1 has been shown to
1365:Topoisomerase inhibitor
1326:Topoisomerase inhibitor
718:supercoiled DNA binding
2659:10.1073/pnas.080536597
2596:10.1073/pnas.022631899
2488:10.1074/jbc.271.4.1993
2426:Nucleic Acids Research
2300:10.1093/nar/26.12.2955
2288:Nucleic Acids Research
1484:There are a number of
865:DNA topological change
835:chromosome segregation
514:pancreatic ductal cell
2438:10.1093/nar/26.7.1841
2388:10.1186/1471-2164-3-1
1396:epigenetic alteration
1344:Camptotheca acuminata
820:programmed cell death
564:mandibular prominence
257:Chromosome 20 (human)
1607:Type I topoisomerase
1261:at the -1 position.
810:chromatin remodeling
560:maxillary prominence
398:2 H2|2 80.96 cM
359:Chromosome 2 (mouse)
78:List of PDB id codes
51:Available structures
2650:2000PNAS...97.4046M
2587:2002PNAS...99.1235M
2528:1999PNAS...9610355G
2066:2014PLoSO...9j8483P
2004:2006PNAS..103.8822A
1831:2012PNAS..10916125S
1388:Synthetic lethality
1383:Synthetic lethality
1302:transesterification
1278:and there are four
1214:DNA topoisomerase 1
840:protein sumoylation
794:protein-DNA complex
584:ganglionic eminence
494:ganglionic eminence
2221:10.1111/acel.12525
1780:Annu. Rev. Biochem
1715:Pommier Y (2013).
1443:colorectal cancers
1354:. Irinotecan and
1000:ENSMUSG00000070544
815:embryonic cleavage
803:Biological process
764:nuclear chromosome
732:Cellular component
663:isomerase activity
646:Molecular function
2983:
2982:
2172:10.4161/cbt.23759
2160:Cancer Biol. Ther
2122:(12): 3087–3096.
1942:10.1002/ijc.30509
1893:10.1002/med.21342
1733:10.1021/cb300648v
1229:DNA topoisomerase
1211:
1210:
1207:
1206:
1180:
1179:
1145:
1144:
1124:
1123:
1098:
1097:
1077:
1076:
1051:
1050:
1032:
1031:
1006:
1005:
987:
986:
961:
960:
942:
941:
890:
889:
658:chromatin binding
630:
629:
626:
625:
604:
603:
591:
590:
529:
528:
427:
426:
326:
325:
153:
152:
149:
148:
61:Ortholog search:
16:(Redirected from
3003:
2969:
2954:
2939:
2924:
2909:
2894:
2879:
2864:
2849:
2834:
2819:
2804:
2789:
2774:
2759:
2739:
2732:
2725:
2716:
2682:
2681:
2671:
2661:
2625:
2619:
2618:
2608:
2598:
2566:
2560:
2559:
2549:
2539:
2522:(18): 10355–60.
2507:
2501:
2500:
2490:
2466:
2460:
2459:
2449:
2417:
2411:
2410:
2400:
2390:
2366:
2357:
2356:
2328:
2322:
2321:
2311:
2279:
2273:
2272:
2252:
2243:
2242:
2232:
2200:
2194:
2193:
2183:
2151:
2142:
2141:
2131:
2116:Mol. Cancer Ther
2107:
2098:
2097:
2087:
2077:
2045:
2036:
2035:
2025:
2015:
1983:
1972:
1971:
1961:
1921:
1915:
1914:
1904:
1872:
1863:
1862:
1852:
1842:
1825:(40): 16125–30.
1810:
1804:
1803:
1775:
1769:
1768:
1761:
1755:
1754:
1744:
1712:
1699:
1698:
1687:
1681:
1680:
1669:
1663:
1653:
1642:
1632:
1258:topoisomerases I
1193:
1192:
1164:
1157:
1140:
1128:
1119:
1107:
1103:RefSeq (protein)
1093:
1081:
1072:
1060:
1036:
1017:
991:
972:
946:
927:
896:
855:circadian rhythm
830:rhythmic process
774:fibrillar center
636:
615:
600:
580:ventricular zone
576:genital tubercle
556:secondary oocyte
548:Ileal epithelium
540:
538:Top expressed in
533:
498:secondary oocyte
490:ventricular zone
478:
476:Top expressed in
471:
450:
433:
423:
410:
399:
384:
377:
371:
360:
348:
332:
322:
309:
298:
283:
276:
270:
259:
245:
229:
223:
221:TOP1 - orthologs
174:
167:
144:
75:
69:
48:
47:
42:
30:
21:
3011:
3010:
3006:
3005:
3004:
3002:
3001:
3000:
2986:
2985:
2984:
2979:
2976:
2970:
2961:
2955:
2946:
2940:
2931:
2925:
2916:
2910:
2901:
2895:
2886:
2880:
2871:
2865:
2856:
2850:
2841:
2835:
2826:
2820:
2811:
2805:
2796:
2790:
2781:
2775:
2766:
2760:
2746:
2743:
2690:
2685:
2627:
2626:
2622:
2568:
2567:
2563:
2509:
2508:
2504:
2468:
2467:
2463:
2419:
2418:
2414:
2368:
2367:
2360:
2330:
2329:
2325:
2294:(12): 2955–62.
2281:
2280:
2276:
2257:Cancer Research
2254:
2253:
2246:
2202:
2201:
2197:
2153:
2152:
2145:
2109:
2108:
2101:
2060:(10): e108483.
2047:
2046:
2039:
1985:
1984:
1975:
1923:
1922:
1918:
1874:
1873:
1866:
1812:
1811:
1807:
1777:
1776:
1772:
1763:
1762:
1758:
1714:
1713:
1702:
1689:
1688:
1684:
1671:
1670:
1666:
1654:
1645:
1633:
1624:
1620:
1603:
1598:
1551:
1531:
1520:) expression.
1500:hypermethylated
1412:hypermethylated
1385:
1373:
1328:
1322:
1256:The eukaryotic
1250:
1241:
1202:View/Edit Mouse
1197:View/Edit Human
1160:
1153:
1150:Location (UCSC)
1136:
1115:
1089:
1068:
981:ENSG00000198900
874:
850:DNA replication
825:phosphorylation
798:
727:
678:protein binding
596:
587:
582:
578:
574:
570:
566:
562:
558:
554:
550:
536:
525:
520:
516:
512:
508:
504:
500:
496:
492:
488:
474:
418:
405:
397:
387:
386:
385:
378:
358:
335:Gene location (
317:
304:
296:
286:
285:
284:
277:
255:
232:Gene location (
183:
170:
163:
84:
62:
28:
23:
22:
18:Topoisomerase I
15:
12:
11:
5:
3009:
3007:
2999:
2998:
2988:
2987:
2981:
2980:
2978:
2977:
2971:
2964:
2962:
2956:
2949:
2947:
2941:
2934:
2932:
2926:
2919:
2917:
2911:
2904:
2902:
2896:
2889:
2887:
2881:
2874:
2872:
2866:
2859:
2857:
2851:
2844:
2842:
2836:
2829:
2827:
2821:
2814:
2812:
2806:
2799:
2797:
2791:
2784:
2782:
2776:
2769:
2767:
2761:
2754:
2751:
2748:
2747:
2744:
2742:
2741:
2734:
2727:
2719:
2713:
2712:
2689:
2688:External links
2686:
2684:
2683:
2644:(8): 4046–51.
2620:
2581:(3): 1235–40.
2561:
2502:
2461:
2412:
2358:
2323:
2274:
2244:
2195:
2143:
2099:
2037:
1998:(23): 8822–7.
1973:
1936:(4): 930–937.
1916:
1864:
1805:
1770:
1756:
1721:ACS Chem. Biol
1700:
1682:
1664:
1643:
1621:
1619:
1616:
1615:
1614:
1609:
1602:
1599:
1597:
1596:
1590:
1584:
1578:
1572:
1566:
1559:
1550:
1547:
1530:
1527:
1498:is frequently
1384:
1381:
1372:
1369:
1324:Main article:
1321:
1318:
1282:and sites for
1249:
1246:
1240:
1237:
1209:
1208:
1205:
1204:
1199:
1189:
1188:
1182:
1181:
1178:
1177:
1175:
1173:
1166:
1165:
1158:
1151:
1147:
1146:
1143:
1142:
1132:
1131:
1125:
1122:
1121:
1111:
1110:
1104:
1100:
1099:
1096:
1095:
1085:
1084:
1078:
1075:
1074:
1064:
1063:
1057:
1053:
1052:
1049:
1048:
1040:
1039:
1033:
1030:
1029:
1021:
1020:
1014:
1008:
1007:
1004:
1003:
995:
994:
988:
985:
984:
976:
975:
969:
963:
962:
959:
958:
950:
949:
943:
940:
939:
931:
930:
924:
918:
917:
912:
907:
903:
902:
892:
891:
888:
887:
876:
875:
873:
872:
867:
862:
857:
852:
847:
842:
837:
832:
827:
822:
817:
812:
806:
804:
800:
799:
797:
796:
791:
786:
781:
776:
771:
766:
761:
756:
751:
746:
741:
735:
733:
729:
728:
726:
725:
720:
715:
710:
705:
700:
695:
690:
685:
680:
675:
670:
665:
660:
655:
649:
647:
643:
642:
632:
631:
628:
627:
624:
623:
620:
619:
612:
606:
605:
602:
601:
593:
592:
589:
588:
586:
585:
581:
577:
573:
569:
568:tail of embryo
565:
561:
557:
553:
549:
545:
542:
541:
530:
527:
526:
524:
523:
519:
515:
511:
507:
503:
499:
495:
491:
487:
483:
480:
479:
467:
466:
458:
447:
441:
440:
437:RNA expression
429:
428:
425:
424:
416:
412:
411:
403:
400:
395:
389:
388:
379:
372:
366:
362:
361:
356:
350:
349:
341:
340:
328:
327:
324:
323:
315:
311:
310:
302:
299:
294:
288:
287:
278:
271:
265:
261:
260:
253:
247:
246:
238:
237:
225:
224:
181:
177:
176:
168:
160:
159:
155:
154:
151:
150:
147:
146:
80:
79:
71:
70:
59:
53:
52:
44:
43:
35:
34:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
3008:
2997:
2994:
2993:
2991:
2974:
2968:
2963:
2959:
2953:
2948:
2944:
2938:
2933:
2929:
2923:
2918:
2914:
2908:
2903:
2899:
2893:
2888:
2884:
2878:
2873:
2869:
2863:
2858:
2854:
2848:
2843:
2839:
2833:
2828:
2824:
2818:
2813:
2809:
2803:
2798:
2794:
2788:
2783:
2779:
2773:
2768:
2764:
2758:
2753:
2749:
2740:
2735:
2733:
2728:
2726:
2721:
2720:
2717:
2710:
2706:
2705:
2700:
2696:
2692:
2691:
2687:
2679:
2675:
2670:
2665:
2660:
2655:
2651:
2647:
2643:
2639:
2635:
2631:
2624:
2621:
2616:
2612:
2607:
2602:
2597:
2592:
2588:
2584:
2580:
2576:
2572:
2565:
2562:
2557:
2553:
2548:
2543:
2538:
2533:
2529:
2525:
2521:
2517:
2513:
2506:
2503:
2498:
2494:
2489:
2484:
2481:(4): 1993–7.
2480:
2476:
2472:
2465:
2462:
2457:
2453:
2448:
2443:
2439:
2435:
2432:(7): 1841–7.
2431:
2427:
2423:
2416:
2413:
2408:
2404:
2399:
2394:
2389:
2384:
2380:
2376:
2372:
2365:
2363:
2359:
2354:
2350:
2346:
2342:
2339:(4): 677–86.
2338:
2334:
2327:
2324:
2319:
2315:
2310:
2305:
2301:
2297:
2293:
2289:
2285:
2278:
2275:
2270:
2266:
2263:(5): 976–84.
2262:
2258:
2251:
2249:
2245:
2240:
2236:
2231:
2226:
2222:
2218:
2214:
2210:
2206:
2199:
2196:
2191:
2187:
2182:
2177:
2173:
2169:
2166:(5): 401–10.
2165:
2161:
2157:
2150:
2148:
2144:
2139:
2135:
2130:
2125:
2121:
2117:
2113:
2106:
2104:
2100:
2095:
2091:
2086:
2081:
2076:
2071:
2067:
2063:
2059:
2055:
2051:
2044:
2042:
2038:
2033:
2029:
2024:
2019:
2014:
2009:
2005:
2001:
1997:
1993:
1989:
1982:
1980:
1978:
1974:
1969:
1965:
1960:
1955:
1951:
1947:
1943:
1939:
1935:
1931:
1927:
1920:
1917:
1912:
1908:
1903:
1898:
1894:
1890:
1887:(4): 753–89.
1886:
1882:
1878:
1871:
1869:
1865:
1860:
1856:
1851:
1846:
1841:
1836:
1832:
1828:
1824:
1820:
1816:
1809:
1806:
1801:
1797:
1793:
1789:
1785:
1781:
1774:
1771:
1766:
1760:
1757:
1752:
1748:
1743:
1738:
1734:
1730:
1726:
1722:
1718:
1711:
1709:
1707:
1705:
1701:
1696:
1692:
1686:
1683:
1678:
1674:
1668:
1665:
1661:
1657:
1652:
1650:
1648:
1644:
1640:
1636:
1631:
1629:
1627:
1623:
1617:
1613:
1612:Topoisomerase
1610:
1608:
1605:
1604:
1600:
1594:
1591:
1588:
1585:
1582:
1579:
1576:
1573:
1570:
1567:
1564:
1561:
1560:
1558:
1556:
1548:
1546:
1544:
1540:
1536:
1528:
1526:
1523:
1519:
1518:
1512:
1509:
1505:
1501:
1497:
1496:
1491:
1487:
1482:
1480:
1476:
1472:
1468:
1464:
1460:
1457:
1453:
1452:
1446:
1444:
1440:
1436:
1432:
1428:
1424:
1420:
1416:
1413:
1409:
1408:
1402:
1399:
1397:
1393:
1389:
1382:
1380:
1378:
1370:
1368:
1366:
1362:
1357:
1353:
1349:
1345:
1341:
1337:
1333:
1327:
1319:
1317:
1315:
1311:
1307:
1303:
1298:
1296:
1293:
1289:
1285:
1281:
1277:
1276:
1271:
1267:
1262:
1259:
1254:
1247:
1245:
1238:
1236:
1234:
1230:
1226:
1223:
1219:
1215:
1203:
1198:
1194:
1190:
1187:
1183:
1176:
1174:
1171:
1167:
1163:
1159:
1156:
1152:
1148:
1141:
1139:
1133:
1129:
1126:
1120:
1118:
1112:
1108:
1105:
1101:
1094:
1092:
1086:
1082:
1079:
1073:
1071:
1065:
1061:
1058:
1056:RefSeq (mRNA)
1054:
1047:
1046:
1041:
1037:
1034:
1028:
1027:
1022:
1018:
1015:
1013:
1009:
1002:
1001:
996:
992:
989:
983:
982:
977:
973:
970:
968:
964:
957:
956:
951:
947:
944:
938:
937:
932:
928:
925:
923:
919:
916:
913:
911:
908:
904:
901:
897:
893:
886:
882:
877:
871:
868:
866:
863:
861:
860:viral process
858:
856:
853:
851:
848:
846:
843:
841:
838:
836:
833:
831:
828:
826:
823:
821:
818:
816:
813:
811:
808:
807:
805:
802:
801:
795:
792:
790:
787:
785:
782:
780:
777:
775:
772:
770:
767:
765:
762:
760:
757:
755:
752:
750:
747:
745:
742:
740:
737:
736:
734:
731:
730:
724:
721:
719:
716:
714:
711:
709:
706:
704:
701:
699:
696:
694:
691:
689:
686:
684:
681:
679:
676:
674:
671:
669:
666:
664:
661:
659:
656:
654:
651:
650:
648:
645:
644:
641:
640:Gene ontology
637:
633:
621:
616:
613:
611:
607:
599:
594:
583:
579:
575:
571:
567:
563:
559:
555:
551:
547:
546:
543:
539:
534:
531:
521:
517:
513:
509:
505:
501:
497:
493:
489:
485:
484:
481:
477:
472:
469:
468:
465:
463:
459:
457:
456:
452:
451:
448:
446:
442:
438:
434:
430:
422:
417:
413:
409:
404:
394:
390:
383:
376:
370:
363:
355:
351:
347:
342:
338:
333:
329:
321:
316:
312:
308:
303:
293:
289:
282:
275:
269:
262:
258:
252:
248:
244:
239:
235:
230:
226:
222:
218:
214:
210:
206:
202:
198:
194:
190:
186:
178:
173:
166:
161:
156:
145:
143:
139:
135:
131:
127:
123:
119:
115:
111:
107:
103:
99:
95:
91:
87:
81:
76:
73:
72:
68:
65:
58:
54:
49:
45:
41:
36:
31:
19:
2972:
2957:
2942:
2927:
2912:
2897:
2882:
2867:
2852:
2837:
2822:
2807:
2792:
2777:
2762:
2702:
2641:
2637:
2632:(Apr 2000).
2623:
2578:
2574:
2564:
2519:
2515:
2505:
2478:
2474:
2464:
2429:
2425:
2415:
2378:
2375:BMC Genomics
2374:
2336:
2332:
2326:
2291:
2287:
2277:
2260:
2256:
2215:(1): 52–60.
2212:
2208:
2198:
2163:
2159:
2119:
2115:
2057:
2053:
1995:
1991:
1933:
1929:
1919:
1884:
1880:
1822:
1818:
1808:
1783:
1779:
1773:
1759:
1727:(1): 82–95.
1724:
1720:
1694:
1685:
1676:
1667:
1552:
1549:Interactions
1532:
1521:
1515:
1513:
1507:
1494:
1486:pre-clinical
1483:
1481:deficiency.
1478:
1474:
1470:
1466:
1449:
1447:
1438:
1434:
1430:
1426:
1422:
1414:
1406:
1403:
1400:
1386:
1374:
1361:Camptothecin
1343:
1340:camptothecin
1329:
1310:supercoiling
1299:
1273:
1270:supercoiling
1263:
1255:
1251:
1242:
1221:
1213:
1212:
1135:
1114:
1088:
1067:
1043:
1024:
998:
979:
953:
934:
914:
909:
460:
453:
419:160,564,684
406:160,487,808
180:External IDs
83:
2745:PDB gallery
1881:Med Res Rev
1786:: 369–413.
1306:nucleophile
1292:active site
779:nucleoplasm
708:ATP binding
688:DNA binding
683:RNA binding
572:human fetus
502:pericardium
318:41,124,487
305:41,028,822
158:Identifiers
2209:Aging Cell
1662:, May 2017
1641:, May 2017
1618:References
1529:DNA repair
1490:epigenetic
1421:(silenced
1336:irinotecan
1332:inhibitors
1320:Inhibition
1314:religation
1266:N-terminal
1227:. It is a
759:chromosome
744:perikaryon
464:(ortholog)
201:HomoloGene
1950:1097-0215
1581:Nucleolin
1419:promoters
1377:topotecan
1348:metabolic
1272:activity
1248:Mechanism
1138:NP_033434
1117:NP_003277
1091:NM_009408
1070:NM_003286
900:Orthologs
784:nucleolus
739:cytoplasm
510:vena cava
209:GeneCards
2990:Category
2678:10759568
2615:11805286
2556:10468612
2407:11818025
2353:12270705
2239:27618784
2190:23377825
2138:27638859
2094:25310185
2054:PLOS ONE
2032:16723399
1968:27859136
1911:25808858
1859:22991469
1800:11395412
1751:23259582
1658:–
1637:–
1601:See also
1555:interact
1508:in vitro
1456:adjuvant
1392:mutation
1350:product
1288:tyrosine
1275:in vitro
1239:Function
1186:Wikidata
879:Sources:
522:monocyte
2709:PDBe-KB
2699:UniProt
2646:Bibcode
2583:Bibcode
2524:Bibcode
2497:8567649
2456:9512561
2318:9611241
2269:9500459
2230:5242303
2181:3672184
2085:4195600
2062:Bibcode
2023:1466544
2000:Bibcode
1959:5299512
1902:4465867
1850:3479559
1827:Bibcode
1742:3549721
1660:Ensembl
1639:Ensembl
1563:ASF/SF2
1012:UniProt
967:Ensembl
906:Species
885:QuickGO
769:nucleus
506:pylorus
439:pattern
165:Aliases
2704:P11387
2676:
2666:
2630:Liu LF
2613:
2606:122173
2603:
2554:
2544:
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2447:147454
2444:
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2309:147637
2306:
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2178:
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2082:
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2020:
1966:
1956:
1948:
1909:
1899:
1857:
1847:
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1739:
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1371:Cancer
1218:enzyme
1216:is an
1172:search
1170:PubMed
1045:Q04750
1026:P11387
922:Entrez
749:P-body
610:BioGPS
552:zygote
486:oocyte
189:126420
2669:18143
2547:17892
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1593:UBE2I
1575:BTBD2
1569:BTBD1
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1517:NDRG1
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1471:MRE11
1467:MRE11
1463:MRE11
1459:bolus
1451:MRE11
1417:gene
1356:SN-38
1352:SN-38
955:21969
915:Mouse
910:Human
881:Amigo
462:Mouse
455:Human
402:Start
337:Mouse
301:Start
297:20q12
234:Human
197:98788
2973:1tl8
2958:1t8i
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2913:1rrj
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2793:1a36
2778:1a35
2763:1a31
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2552:PMID
2493:PMID
2452:PMID
2403:PMID
2349:PMID
2314:PMID
2265:PMID
2235:PMID
2186:PMID
2134:PMID
2090:PMID
2028:PMID
1964:PMID
1946:ISSN
1907:PMID
1855:PMID
1796:PMID
1747:PMID
1225:gene
1222:TOP1
936:7150
445:Bgee
393:Band
354:Chr.
292:Band
251:Chr.
213:TOP1
205:2467
185:OMIM
172:TOP1
142:1TL8
138:1T8I
134:1SEU
130:1SC7
126:1RRJ
122:1RR8
118:1R49
114:1NH3
110:1LPQ
106:1K4T
102:1K4S
98:1EJ9
94:1A36
90:1A35
86:1A31
67:RCSB
64:PDBe
33:TOP1
2695:PDB
2664:PMC
2654:doi
2601:PMC
2591:doi
2542:PMC
2532:doi
2483:doi
2479:271
2442:PMC
2434:doi
2393:PMC
2383:doi
2341:doi
2337:322
2304:PMC
2296:doi
2225:PMC
2217:doi
2176:PMC
2168:doi
2124:doi
2080:PMC
2070:doi
2018:PMC
2008:doi
1996:103
1954:PMC
1938:doi
1934:140
1897:PMC
1889:doi
1845:PMC
1835:doi
1823:109
1788:doi
1737:PMC
1729:doi
1587:P53
1539:DNA
1535:UVB
1495:ATM
1439:WRN
1435:WRN
1431:WRN
1427:WRN
1423:WRN
1415:WRN
1407:WRN
1295:Tyr
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618:n/a
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314:End
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