Identification and characterization of topoisomerase III beta poisons

We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular Cytotoxicity Screen. We found a bisacridine compound NSC690634 and a thiacyanine compound NSC96932 that preferentially sensitize cell lines express...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 120; no. 34; p. e2218483120
Main Authors Wang, Wenjie, Saha, Sourav, Yang, Xi, Pommier, Yves, Huang, Shar-Yin N
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 22.08.2023
Subjects
Biological Sciences
Cell Line
Cell lines
Cytotoxicity
DNA topoisomerase III
DNA Topoisomerases, Type I - metabolism
Lead compounds
Poisons
R-loops
RNA
Topoisomerase I Inhibitors - chemistry
TOP3B
anti-cancer
inhibitor screen
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Abstract We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular Cytotoxicity Screen. We found a bisacridine compound NSC690634 and a thiacyanine compound NSC96932 that preferentially sensitize cell lines expressing TOP3B, indicating that they target TOP3B. These compounds trap TOP3B cleavage complex (TOP3Bcc) in cells and in vitro and predominately act on RNA, leading to high levels of RNA-TOP3Bccs. NSC690634 also leads to enhanced R-loops in a TOP3B-dependent manner. Preliminary structural activity studies show that the lengths of linkers between the two aromatic moieties in each compound are critical; altering the linker length completely abolishes the trapping of TOP3Bccs. Both of our lead compounds share a similar structural motif, which can serve as a base for further modification. They may also serve in anticancer, antiviral, and/or basic research applications.
AbstractList We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular Cytotoxicity Screen. We found a bisacridine compound NSC690634 and a thiacyanine compound NSC96932 that preferentially sensitize cell lines expressing TOP3B, indicating that they target TOP3B. These compounds trap TOP3B cleavage complex (TOP3Bcc) in cells and in vitro and predominately act on RNA, leading to high levels of RNA-TOP3Bccs. NSC690634 also leads to enhanced R-loops in a TOP3B-dependent manner. Preliminary structural activity studies show that the lengths of linkers between the two aromatic moieties in each compound are critical; altering the linker length completely abolishes the trapping of TOP3Bccs. Both of our lead compounds share a similar structural motif, which can serve as a base for further modification. They may also serve in anticancer, antiviral, and/or basic research applications.
Topoisomerase poisons that trap topoisomerase I and II (TOP1 and TOP2) have long been important agents in anticancer therapy and for elucidating the cellular functions of TOP1 and TOP2. However, poisons for topoisomerase III have never been reported. Topoisomerase III beta (TOP3B) is the only topoisomerase with a dual activity on RNA as well as DNA and has recently been reported to ensure genome stability, chromatin accessibility, R-loops resolution, and potentially the replication of positive-sense RNA viruses, including dengue and SARS-CoV-2. In our study, we designed and carried out a chemical screen for poisons that trap human TOP3B. Among the most active inhibitors, we report and characterize in vitro and cellular trapping of TOP3B by bisacridine and thiacyanine compounds. We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular Cytotoxicity Screen. We found a bisacridine compound NSC690634 and a thiacyanine compound NSC96932 that preferentially sensitize cell lines expressing TOP3B, indicating that they target TOP3B. These compounds trap TOP3B cleavage complex (TOP3Bcc) in cells and in vitro and predominately act on RNA, leading to high levels of RNA-TOP3Bccs. NSC690634 also leads to enhanced R-loops in a TOP3B-dependent manner. Preliminary structural activity studies show that the lengths of linkers between the two aromatic moieties in each compound are critical; altering the linker length completely abolishes the trapping of TOP3Bccs. Both of our lead compounds share a similar structural motif, which can serve as a base for further modification. They may also serve in anticancer, antiviral, and/or basic research applications.
Author Pommier, Yves
Huang, Shar-Yin N
Wang, Wenjie
Yang, Xi
Saha, Sourav
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10.1073/pnas.81.5.1361
10.1016/j.celrep.2020.108569
10.1038/nn.3479
10.1111/j.1755-148X.2009.00545.x
10.1016/j.celrep.2022.111067
10.1021/ar030257c
10.1128/AAC.01418-06
10.1016/0277-5379(88)90082-X
10.1098/rsob.190222
10.1038/s41467-019-08942-3
10.1021/jm00207a006
10.1021/cb300648v
10.1038/s41596-019-0159-1
10.1021/bi00526a006
10.1093/nar/gkw508
10.1016/j.ymeth.2019.09.013
10.1016/j.phrs.2021.105927
10.1038/nn.3484
10.1038/s41580-022-00452-3
10.1158/1078-0432.CCR-15-0335
10.1093/nar/gkt171
10.1016/j.cell.2018.11.004
10.1038/nrd3404
10.1046/j.1472-765X.1998.00357.x
10.1016/j.antiviral.2020.104874
10.1126/sciadv.aba6290
10.1016/j.jmb.2019.07.008
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anti-cancer
inhibitor screen
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1W.W. and S.S. contributed equally to this work.
Edited by Anthony Maxwell, John Innes Centre, Norwich, United Kingdom; received October 29, 2022; accepted July 17, 2023 by Editorial Board Member Rodney Rothstein
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References e_1_3_4_3_2
e_1_3_4_2_2
e_1_3_4_1_2
e_1_3_4_8_2
e_1_3_4_7_2
e_1_3_4_6_2
e_1_3_4_5_2
e_1_3_4_4_2
e_1_3_4_22_2
e_1_3_4_23_2
e_1_3_4_20_2
e_1_3_4_21_2
e_1_3_4_26_2
e_1_3_4_27_2
e_1_3_4_24_2
e_1_3_4_25_2
e_1_3_4_28_2
e_1_3_4_29_2
Ahmad M. (e_1_3_4_9_2) 2017; 45
e_1_3_4_11_2
e_1_3_4_12_2
e_1_3_4_10_2
e_1_3_4_15_2
e_1_3_4_16_2
e_1_3_4_13_2
e_1_3_4_14_2
e_1_3_4_19_2
e_1_3_4_17_2
e_1_3_4_18_2
References_xml – ident: e_1_3_4_17_2
  doi: 10.1016/0003-2697(75)90498-4
– volume: 45
  start-page: 2704
  year: 2017
  ident: e_1_3_4_9_2
  article-title: Topoisomerase 3beta is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction
  publication-title: Nucleic Acids Res.
  contributor:
    fullname: Ahmad M.
– ident: e_1_3_4_22_2
  doi: 10.1073/pnas.81.5.1361
– ident: e_1_3_4_11_2
  doi: 10.1016/j.celrep.2020.108569
– ident: e_1_3_4_6_2
  doi: 10.1038/nn.3479
– ident: e_1_3_4_25_2
  doi: 10.1111/j.1755-148X.2009.00545.x
– ident: e_1_3_4_7_2
  doi: 10.1016/j.celrep.2022.111067
– ident: e_1_3_4_24_2
  doi: 10.1021/ar030257c
– ident: e_1_3_4_19_2
  doi: 10.1128/AAC.01418-06
– ident: e_1_3_4_21_2
  doi: 10.1016/0277-5379(88)90082-X
– ident: e_1_3_4_10_2
  doi: 10.1098/rsob.190222
– ident: e_1_3_4_27_2
  doi: 10.1038/s41467-019-08942-3
– ident: e_1_3_4_20_2
  doi: 10.1021/jm00207a006
– ident: e_1_3_4_3_2
  doi: 10.1021/cb300648v
– ident: e_1_3_4_29_2
  doi: 10.1038/s41596-019-0159-1
– ident: e_1_3_4_23_2
  doi: 10.1021/bi00526a006
– ident: e_1_3_4_8_2
  doi: 10.1093/nar/gkw508
– ident: e_1_3_4_28_2
  doi: 10.1016/j.ymeth.2019.09.013
– ident: e_1_3_4_12_2
  doi: 10.1016/j.phrs.2021.105927
– ident: e_1_3_4_5_2
  doi: 10.1038/nn.3484
– ident: e_1_3_4_1_2
  doi: 10.1038/s41580-022-00452-3
– ident: e_1_3_4_14_2
  doi: 10.1158/1078-0432.CCR-15-0335
– ident: e_1_3_4_15_2
  doi: 10.1093/nar/gkt171
– ident: e_1_3_4_26_2
  doi: 10.1016/j.cell.2018.11.004
– ident: e_1_3_4_2_2
  doi: 10.1038/nrd3404
– ident: e_1_3_4_18_2
  doi: 10.1046/j.1472-765X.1998.00357.x
– ident: e_1_3_4_13_2
  doi: 10.1016/j.antiviral.2020.104874
– ident: e_1_3_4_16_2
  doi: 10.1126/sciadv.aba6290
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Snippet We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular...
Topoisomerase poisons that trap topoisomerase I and II (TOP1 and TOP2) have long been important agents in anticancer therapy and for elucidating the cellular...
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SubjectTerms Biological Sciences
Cell Line
Cell lines
Cytotoxicity
DNA topoisomerase III
DNA Topoisomerases, Type I - metabolism
Lead compounds
Poisons
R-loops
RNA
Topoisomerase I Inhibitors - chemistry
Title Identification and characterization of topoisomerase III beta poisons
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