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SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin.
Oncogene. 2002 Nov 14; 21(52):7913-22.O

Abstract

DNA topoisomerase I (Topo1) manages the topological state of DNA. Cleavable complexes, the covalent Topo1-DNA intermediates, become DNA damaged when the catalytic cycles are inhibited by the anti-tumor drug camptothecin (CPT). Intriguingly, Topo1 is modified rapidly and extensively with SUMO-1, a ubiquitin-like protein, in response to CPT. This study shows that the sumoylation enhances the cleavable complex formation and apoptosis induced by CPT. Indeed, substitutions of Lys117 and Lys153, identified as Topo1 sumoylation sites, reduced the CPT-induced cleavable complexes without influencing its in vitro catalytic activity. Consistent with this observation, CPT-induced cleavable complexes of wild-type Topo1 increased in a sumoylation-dependent manner. We also found that Topo1 sumoylation occurred independently of CPT when Topo1 was inactivated by mutation of the catalytic Tyr723. These findings suggested that Topo1 inactivation by CPT treatment can trigger Topo1 sumoylation, leading to enhanced cleavable complex formation.

Authors+Show Affiliations

Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12439742

Citation

Horie, Koji, et al. "SUMO-1 Conjugation to Intact DNA Topoisomerase I Amplifies Cleavable Complex Formation Induced By Camptothecin." Oncogene, vol. 21, no. 52, 2002, pp. 7913-22.
Horie K, Tomida A, Sugimoto Y, et al. SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin. Oncogene. 2002;21(52):7913-22.
Horie, K., Tomida, A., Sugimoto, Y., Yasugi, T., Yoshikawa, H., Taketani, Y., & Tsuruo, T. (2002). SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin. Oncogene, 21(52), 7913-22.
Horie K, et al. SUMO-1 Conjugation to Intact DNA Topoisomerase I Amplifies Cleavable Complex Formation Induced By Camptothecin. Oncogene. 2002 Nov 14;21(52):7913-22. PubMed PMID: 12439742.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin. AU - Horie,Koji, AU - Tomida,Akihiro, AU - Sugimoto,Yoshikazu, AU - Yasugi,Toshiharu, AU - Yoshikawa,Hiroyuki, AU - Taketani,Yuji, AU - Tsuruo,Takashi, PY - 2002/05/13/received PY - 2002/07/19/revised PY - 2002/07/25/accepted PY - 2002/11/20/pubmed PY - 2002/12/5/medline PY - 2002/11/20/entrez SP - 7913 EP - 22 JF - Oncogene JO - Oncogene VL - 21 IS - 52 N2 - DNA topoisomerase I (Topo1) manages the topological state of DNA. Cleavable complexes, the covalent Topo1-DNA intermediates, become DNA damaged when the catalytic cycles are inhibited by the anti-tumor drug camptothecin (CPT). Intriguingly, Topo1 is modified rapidly and extensively with SUMO-1, a ubiquitin-like protein, in response to CPT. This study shows that the sumoylation enhances the cleavable complex formation and apoptosis induced by CPT. Indeed, substitutions of Lys117 and Lys153, identified as Topo1 sumoylation sites, reduced the CPT-induced cleavable complexes without influencing its in vitro catalytic activity. Consistent with this observation, CPT-induced cleavable complexes of wild-type Topo1 increased in a sumoylation-dependent manner. We also found that Topo1 sumoylation occurred independently of CPT when Topo1 was inactivated by mutation of the catalytic Tyr723. These findings suggested that Topo1 inactivation by CPT treatment can trigger Topo1 sumoylation, leading to enhanced cleavable complex formation. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/12439742/SUMO_1_conjugation_to_intact_DNA_topoisomerase_I_amplifies_cleavable_complex_formation_induced_by_camptothecin_ L2 - https://doi.org/10.1038/sj.onc.1205917 DB - PRIME DP - Unbound Medicine ER -