Suppressing proteasome mediated processing of topoisomerase II DNA-protein complexes preserves genome integrity

Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the c...

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Published ineLife Vol. 9
Main Authors Sciascia, Nicholas, Wu, Wei, Zong, Dali, Sun, Yilun, Wong, Nancy, John, Sam, Wangsa, Darawalee, Ried, Thomas, Bunting, Samuel F, Pommier, Yves, Nussenzweig, André
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Abstract Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are thought to remove TOP2ccs primarily by proteolytic degradation followed by DNA DSB repair. Here, we show that proteasome-mediated repair of TOP2cc is highly error-prone. Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability. When degradation of TOP2cc was suppressed, the TOP2 enzyme uncoupled itself from the DNA following ETO washout, in an error-free manner. This suggests a potential mechanism of developing resistance to topoisomerase poisons by ensuring rapid TOP2cc reversal.
AbstractList Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are thought to remove TOP2ccs primarily by proteolytic degradation followed by DNA DSB repair. Here, we show that proteasome-mediated repair of TOP2cc is highly error-prone. Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability. When degradation of TOP2cc was suppressed, the TOP2 enzyme uncoupled itself from the DNA following ETO washout, in an error-free manner. This suggests a potential mechanism of developing resistance to topoisomerase poisons by ensuring rapid TOP2cc reversal.
Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are thought to remove TOP2ccs primarily by proteolytic degradation followed by DNA DSB repair. Here, we show that proteasome-mediated repair of TOP2cc is highly error-prone. Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability. When degradation of TOP2cc was suppressed, the TOP2 enzyme uncoupled itself from the DNA following ETO washout, in an error-free manner. This suggests a potential mechanism of developing resistance to topoisomerase poisons by ensuring rapid TOP2cc reversal.Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are thought to remove TOP2ccs primarily by proteolytic degradation followed by DNA DSB repair. Here, we show that proteasome-mediated repair of TOP2cc is highly error-prone. Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability. When degradation of TOP2cc was suppressed, the TOP2 enzyme uncoupled itself from the DNA following ETO washout, in an error-free manner. This suggests a potential mechanism of developing resistance to topoisomerase poisons by ensuring rapid TOP2cc reversal.
Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are thought to remove TOP2ccs primarily by proteolytic degradation followed by DNA DSB repair. Here, we show that proteasome-mediated repair of TOP2cc is highly error-prone. Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability. When degradation of TOP2cc was suppressed, the TOP2 enzyme uncoupled itself from the DNA following ETO washout, in an error-free manner. This suggests a potential mechanism of developing resistance to topoisomerase poisons by ensuring rapid TOP2cc reversal. Molecules of DNA contain the archive of a cell’s genetic information and identity. DNA comprises two strands that twist together into a structure known as a double helix. Physical tension tends to build up in the double helix that can cause it to break apart. To avoid this, cells have an enzyme called Topoisomerase II (TOP2) that relieves the tension by attaching itself to DNA and breaking it in a controlled way before re-sealing the break. Drugs known as TOP2 poisons stop TOP2 from working and trap it on the DNA, which may lead to cells accumulating DNA breaks and eventually dying. Cancer cells are particularly prone to acquiring breaks in their DNA, and TOP2 poisons are therefore often used as part of chemotherapy treatments for cancer. However, it remains unclear why TOP2 poisons are more effective at killing some types of cancer cells than others. It is thought that a molecular machine, known as the proteasome, helps cells repair the damage caused by TOP2 poisons by removing the trapped TOP2 proteins and allowing DNA repair proteins access to the broken DNA underneath. Now, Sciascia et al. have used a genetic approach to study the relationship between the proteasome and DNA repair in mouse cells exposed to TOP2 poisons. The experiments found that when the proteasome removed TOP2 proteins that had become trapped on DNA, the subsequent DNA repair was prone to errors. Pre-treating mouse cells with another drug that inhibited the proteasome protected the cells from the effects of the TOP2 poison. Once the TOP2 poison had left the cells, the previously trapped TOP2 proteins correctly fixed the DNA and detached as they would normally. As a result, cells that had been treated with a proteasome inhibitor were more likely to survive treatment with TOP2 poisons. Since both TOP2 poisons and proteasome inhibitors are clinically approved drugs for treating cancer they can be, and already have been, tested for use together in combination drug therapies. However, these findings suggest that caution should be taken when using these drugs together, because instead of harming the cancer cells, the proteasome inhibitors may protect the cells from the toxic effects of TOP2 poisons.
Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are thought to remove TOP2ccs primarily by proteolytic degradation followed by DNA DSB repair. Here, we show that proteasome-mediated repair of TOP2cc is highly error-prone. Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability. When degradation of TOP2cc was suppressed, the TOP2 enzyme uncoupled itself from the DNA following ETO washout, in an error-free manner. This suggests a potential mechanism of developing resistance to topoisomerase poisons by ensuring rapid TOP2cc reversal. eLife digest Molecules of DNA contain the archive of a cell's genetic information and identity. DNA comprises two strands that twist together into a structure known as a double helix. Physical tension tends to build up in the double helix that can cause it to break apart. To avoid this, cells have an enzyme called Topoisomerase II (TOP2) that relieves the tension by attaching itself to DNA and breaking it in a controlled way before re-sealing the break. Drugs known as TOP2 poisons stop TOP2 from working and trap it on the DNA, which may lead to cells accumulating DNA breaks and eventually dying. Cancer cells are particularly prone to acquiring breaks in their DNA, and TOP2 poisons are therefore often used as part of chemotherapy treatments for cancer. However, it remains unclear why TOP2 poisons are more effective at killing some types of cancer cells than others. It is thought that a molecular machine, known as the proteasome, helps cells repair the damage caused by TOP2 poisons by removing the trapped TOP2 proteins and allowing DNA repair proteins access to the broken DNA underneath. Now, Sciascia et al. have used a genetic approach to study the relationship between the proteasome and DNA repair in mouse cells exposed to TOP2 poisons. The experiments found that when the proteasome removed TOP2 proteins that had become trapped on DNA, the subsequent DNA repair was prone to errors. Pre-treating mouse cells with another drug that inhibited the proteasome protected the cells from the effects of the TOP2 poison. Once the TOP2 poison had left the cells, the previously trapped TOP2 proteins correctly fixed the DNA and detached as they would normally. As a result, cells that had been treated with a proteasome inhibitor were more likely to survive treatment with TOP2 poisons. Since both TOP2 poisons and proteasome inhibitors are clinically approved drugs for treating cancer they can be, and already have been, tested for use together in combination drug therapies. However, these findings suggest that caution should be taken when using these drugs together, because instead of harming the cancer cells, the proteasome inhibitors may protect the cells from the toxic effects of TOP2 poisons.
Audience Academic
Author John, Sam
Wangsa, Darawalee
Zong, Dali
Ried, Thomas
Wu, Wei
Sciascia, Nicholas
Sun, Yilun
Pommier, Yves
Wong, Nancy
Nussenzweig, André
Bunting, Samuel F
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Cites_doi 10.1126/science.aam6468
10.1074/jbc.M104009200
10.1186/gb-2008-9-9-r137
10.1371/journal.pone.0005859
10.3892/ol.2016.4340
10.1038/nmeth.1923
10.1016/j.cell.2014.11.021
10.1007/s00280-003-0701-1
10.1093/annonc/mdn018
10.1186/1747-1028-7-26
10.1016/j.yexcr.2009.04.019
10.1124/jpet.106.109397
10.1016/j.molcel.2018.12.010
10.1038/s41467-020-14654-w
10.21873/anticanres.12684
10.1073/pnas.1009025107
10.1371/journal.pgen.1003226
10.1093/bioinformatics/btp352
10.1016/S0021-9258(19)42454-X
10.1038/nature03872
10.1038/nature04866
10.1038/s41467-017-00307-y
10.1101/707661
10.3390/ijms19072056
10.1016/j.cell.2007.06.016
10.1101/gr.229102
10.1667/0033-7587(2003)160[0291:AOTDPK]2.0.CO;2
10.1007/978-1-4939-7459-7_20
10.1038/ng1196-312
10.1124/mol.54.1.78
10.1126/science.292.5521.1552
10.1093/nar/gkh103
10.1016/S1074-5521(01)00056-4
10.1038/nrc2608
10.1016/j.cell.2017.06.034
10.1038/cr.2017.147
10.4161/15384101.2014.950132
10.1080/10428194.2017.1416365
10.1016/j.cell.2013.05.023
10.1038/nrc2607
10.1016/j.molcel.2016.10.011
10.1242/bio.20121834
10.4061/2010/710589
10.1038/nrclinonc.2016.206
10.1101/gad.229559.113
10.3390/ijerph9062075
10.1038/sj.leu.2401812
10.1126/science.1069398
10.1016/j.bcp.2015.12.015
10.1016/j.molcel.2019.04.030
10.1016/S0021-9258(18)81711-2
10.1074/jbc.M604149200
10.1093/bioinformatics/btq033
10.1038/s41467-019-12802-5
10.1038/nature08444
10.1016/S0076-6879(05)99033-2
10.1074/jbc.M803493200
10.1016/j.molcel.2016.06.034
10.3390/ijms150713111
10.1038/nrm.2016.111
10.1186/gb-2009-10-3-r25
10.1016/j.cell.2013.01.006
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Keywords mouse
genetics
genome instability
DNA damage
genomics
cancer
topoisomerases
DNA repair
human
Language English
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PublicationDateYYYYMMDD 2020-02-14
PublicationDate_xml – month: 02
  year: 2020
  text: 2020-02-14
  day: 14
PublicationDecade 2020
PublicationPlace England
PublicationPlace_xml – name: England
– name: Cambridge
PublicationTitle eLife
PublicationTitleAlternate Elife
PublicationYear 2020
Publisher eLife Science Publications, Ltd
eLife Sciences Publications Ltd
eLife Sciences Publications, Ltd
Publisher_xml – name: eLife Science Publications, Ltd
– name: eLife Sciences Publications Ltd
– name: eLife Sciences Publications, Ltd
References Callen (bib10) 2013; 153
Halasi (bib24) 2014; 13
Kisselev (bib30) 2001; 8
Gómez-Herreros (bib22) 2013; 9
Cowell (bib17) 2012; 9
Destanovic (bib18) 2018; 38
Bence (bib6) 2001; 292
Langmead (bib32) 2012; 9
Willmore (bib60) 1998; 54
Neale (bib45) 2005; 436
Barlow (bib5) 2013; 152
Lee (bib36) 2018; 19
Ledesma (bib33) 2009; 461
R Development Core Team (bib52) 2008
Anand (bib2) 2018; 1703
Karolchik (bib28) 2004; 32
Canela (bib12) 2017; 170
Canela (bib13) 2019; 75
Errington (bib20) 2004; 53
Zhang (bib63) 2008; 9
Thomas (bib58) 2017
Nitiss (bib46) 2009; 9
Gómez-Herreros (bib23) 2017; 8
Li (bib37) 2009; 25
Dittus (bib19) 2018; 59
Bence (bib7) 2005
Lee (bib34) 2012; 1
Hu (bib27) 2010; 107
Mao (bib42) 2001; 276
Lee (bib35) 2016; 103
Manasanch (bib41) 2017; 14
Callén (bib9) 2007; 130
Schellenberg (bib55) 2017; 357
Long (bib40) 1985; 45
Pommier (bib50) 2016; 17
Lin (bib38) 2008; 283
Zagnoli-Vieiral (bib61) 2017; 27
Mårtensson (bib43) 2003; 160
von Metzler (bib59) 2009; 315
Kent (bib29) 2002; 12
Bredemeyer (bib8) 2006; 442
Palumbo (bib49) 2008; 19
Baranello (bib4) 2014; 15
Canela (bib11) 2016; 63
Langmead (bib31) 2009; 10
Zhang (bib64) 2013; 27
Muslimović (bib44) 2009; 4
Nitiss (bib47) 2009; 9
Gittens (bib21) 2019; 10
Hsiang (bib26) 1989; 264
Hoa (bib25) 2016; 64
Liyanage (bib39) 1996; 14
Chase (bib16) 1974; 249
Zhang (bib62) 2006; 281
Zong (bib65) 2019; 73
Rastogi (bib54) 2012; 7
Aras (bib3) 2016; 11
Sunter (bib57) 2010; 2010
Celeste (bib14) 2002; 296
Ceruti (bib15) 2006; 319
Paiano (bib48) 2020; 11
Sun (bib56) 2019
Quinlan (bib51) 2010; 26
Rao (bib53) 2014; 159
An (bib1) 2000; 14
References_xml – volume: 45
  start-page: 3106
  year: 1985
  ident: bib40
  article-title: Single- and double-strand DNA breakage and repair in human lung adenocarcinoma cells exposed to etoposide and teniposide
  publication-title: Cancer Research
  contributor:
    fullname: Long
– volume: 357
  start-page: 1412
  year: 2017
  ident: bib55
  article-title: ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links
  publication-title: Science
  doi: 10.1126/science.aam6468
  contributor:
    fullname: Schellenberg
– volume: 276
  start-page: 40652
  year: 2001
  ident: bib42
  article-title: 26 S proteasome-mediated degradation of topoisomerase II cleavable complexes
  publication-title: Journal of Biological Chemistry
  doi: 10.1074/jbc.M104009200
  contributor:
    fullname: Mao
– volume: 9
  year: 2008
  ident: bib63
  article-title: Model-based analysis of ChIP-Seq (MACS)
  publication-title: Genome Biology
  doi: 10.1186/gb-2008-9-9-r137
  contributor:
    fullname: Zhang
– volume-title: R Foundation for Statistical Computing
  year: 2008
  ident: bib52
  article-title: R: A language and environment for statistical computing
  contributor:
    fullname: R Development Core Team
– volume: 4
  year: 2009
  ident: bib44
  article-title: Numerical analysis of etoposide induced DNA breaks
  publication-title: PLOS ONE
  doi: 10.1371/journal.pone.0005859
  contributor:
    fullname: Muslimović
– volume: 11
  start-page: 3179
  year: 2016
  ident: bib3
  article-title: Bortezomib and etoposide combinations exert synergistic effects on the human prostate Cancer cell line PC-3
  publication-title: Oncology Letters
  doi: 10.3892/ol.2016.4340
  contributor:
    fullname: Aras
– volume: 9
  start-page: 357
  year: 2012
  ident: bib32
  article-title: Fast gapped-read alignment with bowtie 2
  publication-title: Nature Methods
  doi: 10.1038/nmeth.1923
  contributor:
    fullname: Langmead
– volume: 159
  start-page: 1665
  year: 2014
  ident: bib53
  article-title: A 3D map of the human genome at Kilobase resolution reveals principles of chromatin looping
  publication-title: Cell
  doi: 10.1016/j.cell.2014.11.021
  contributor:
    fullname: Rao
– volume: 53
  start-page: 155
  year: 2004
  ident: bib20
  article-title: Differences in the longevity of topo iiα and topo iiβ drug-stabilized cleavable complexes and the relationship to drug sensitivity
  publication-title: Cancer Chemotherapy and Pharmacology
  doi: 10.1007/s00280-003-0701-1
  contributor:
    fullname: Errington
– volume: 19
  start-page: 1160
  year: 2008
  ident: bib49
  article-title: Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma
  publication-title: Annals of Oncology
  doi: 10.1093/annonc/mdn018
  contributor:
    fullname: Palumbo
– volume: 7
  year: 2012
  ident: bib54
  article-title: Therapeutic targeting of Cancer cell cycle using proteasome inhibitors
  publication-title: Cell Division
  doi: 10.1186/1747-1028-7-26
  contributor:
    fullname: Rastogi
– volume: 315
  start-page: 2471
  year: 2009
  ident: bib59
  article-title: Synergistic interaction of proteasome and topoisomerase II inhibition in multiple myeloma
  publication-title: Experimental Cell Research
  doi: 10.1016/j.yexcr.2009.04.019
  contributor:
    fullname: von Metzler
– volume: 319
  start-page: 1424
  year: 2006
  ident: bib15
  article-title: Proteasome inhibitors potentiate etoposide-induced cell death in human astrocytoma cells bearing a mutated p53 isoform
  publication-title: Journal of Pharmacology and Experimental Therapeutics
  doi: 10.1124/jpet.106.109397
  contributor:
    fullname: Ceruti
– volume: 73
  start-page: 1267
  year: 2019
  ident: bib65
  article-title: BRCA1 haploinsufficiency is masked by RNF168-Mediated chromatin ubiquitylation
  publication-title: Molecular Cell
  doi: 10.1016/j.molcel.2018.12.010
  contributor:
    fullname: Zong
– volume: 11
  year: 2020
  ident: bib48
  article-title: ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis
  publication-title: Nature Communications
  doi: 10.1038/s41467-020-14654-w
  contributor:
    fullname: Paiano
– volume: 38
  start-page: 3977
  year: 2018
  ident: bib18
  article-title: Preclinical evaluation of combined topoisomerase and proteasome inhibition against pediatric malignancies
  publication-title: Anticancer Research
  doi: 10.21873/anticanres.12684
  contributor:
    fullname: Destanovic
– volume: 107
  start-page: 15087
  year: 2010
  ident: bib27
  article-title: Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen
  publication-title: PNAS
  doi: 10.1073/pnas.1009025107
  contributor:
    fullname: Hu
– volume: 9
  year: 2013
  ident: bib22
  article-title: TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo
  publication-title: PLOS Genetics
  doi: 10.1371/journal.pgen.1003226
  contributor:
    fullname: Gómez-Herreros
– volume: 25
  start-page: 2078
  year: 2009
  ident: bib37
  article-title: The sequence alignment/Map format and SAMtools
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btp352
  contributor:
    fullname: Li
– volume: 249
  start-page: 4553
  year: 1974
  ident: bib16
  article-title: Exonuclease VII of Escherichia coli. Mechanism of action
  publication-title: The Journal of Biological Chemistry
  doi: 10.1016/S0021-9258(19)42454-X
  contributor:
    fullname: Chase
– volume: 436
  start-page: 1053
  year: 2005
  ident: bib45
  article-title: Endonucleolytic processing of covalent protein-linked DNA double-strand breaks
  publication-title: Nature
  doi: 10.1038/nature03872
  contributor:
    fullname: Neale
– volume: 442
  start-page: 466
  year: 2006
  ident: bib8
  article-title: ATM stabilizes DNA double-strand-break complexes during V(D)J recombination
  publication-title: Nature
  doi: 10.1038/nature04866
  contributor:
    fullname: Bredemeyer
– volume: 8
  start-page: 1
  year: 2017
  ident: bib23
  article-title: TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription
  publication-title: Nature Communications
  doi: 10.1038/s41467-017-00307-y
  contributor:
    fullname: Gómez-Herreros
– volume-title: bioRxiv
  year: 2019
  ident: bib56
  article-title: A conserved SUMO-Ubiquitin pathway directed by RNF4/SLX5-SLX8 and PIAS4/SIZ1 drives proteasomal degradation of topoisomerase DNA-protein crosslinks
  doi: 10.1101/707661
  contributor:
    fullname: Sun
– volume: 19
  year: 2018
  ident: bib36
  article-title: Effect of TDP2 on the level of TOP2-DNA complexes and SUMOylated TOP2-DNA complexes
  publication-title: International Journal of Molecular Sciences
  doi: 10.3390/ijms19072056
  contributor:
    fullname: Lee
– volume: 130
  start-page: 63
  year: 2007
  ident: bib9
  article-title: ATM prevents the persistence and propagation of chromosome breaks in lymphocytes
  publication-title: Cell
  doi: 10.1016/j.cell.2007.06.016
  contributor:
    fullname: Callén
– volume: 12
  start-page: 996
  year: 2002
  ident: bib29
  article-title: The human genome browser at UCSC
  publication-title: Genome Research
  doi: 10.1101/gr.229102
  contributor:
    fullname: Kent
– volume: 160
  start-page: 291
  year: 2003
  ident: bib43
  article-title: Activation of the DNA-dependent protein kinase by drug-induced and radiation-induced DNA strand breaks
  publication-title: Radiation Research
  doi: 10.1667/0033-7587(2003)160[0291:AOTDPK]2.0.CO;2
  contributor:
    fullname: Mårtensson
– volume: 1703
  start-page: 283
  year: 2018
  ident: bib2
  article-title: Detection of topoisomerase covalent complexes in eukaryotic cells
  publication-title: Methods in Molecular Biology
  doi: 10.1007/978-1-4939-7459-7_20
  contributor:
    fullname: Anand
– volume: 14
  start-page: 312
  year: 1996
  ident: bib39
  article-title: Multicolour spectral karyotyping of mouse chromosomes
  publication-title: Nature Genetics
  doi: 10.1038/ng1196-312
  contributor:
    fullname: Liyanage
– start-page: 665
  volume-title: Holland-Frei Cancer Medicine
  year: 2017
  ident: bib58
  contributor:
    fullname: Thomas
– volume: 54
  start-page: 78
  year: 1998
  ident: bib60
  article-title: Etoposide targets topoisomerase IIalpha and IIbeta in leukemic cells: isoform-specific cleavable complexes visualized and quantified in situ by a novel immunofluorescence technique
  publication-title: Molecular Pharmacology
  doi: 10.1124/mol.54.1.78
  contributor:
    fullname: Willmore
– volume: 292
  start-page: 1552
  year: 2001
  ident: bib6
  article-title: Impairment of the ubiquitin-proteasome system by protein aggregation
  publication-title: Science
  doi: 10.1126/science.292.5521.1552
  contributor:
    fullname: Bence
– volume: 32
  start-page: 493D
  year: 2004
  ident: bib28
  article-title: The UCSC table browser data retrieval tool
  publication-title: Nucleic Acids Research
  doi: 10.1093/nar/gkh103
  contributor:
    fullname: Karolchik
– volume: 8
  start-page: 739
  year: 2001
  ident: bib30
  article-title: Proteasome inhibitors: from research tools to drug candidates
  publication-title: Chemistry & Biology
  doi: 10.1016/S1074-5521(01)00056-4
  contributor:
    fullname: Kisselev
– volume: 9
  start-page: 327
  year: 2009
  ident: bib46
  article-title: DNA topoisomerase II and its growing repertoire of biological functions
  publication-title: Nature Reviews Cancer
  doi: 10.1038/nrc2608
  contributor:
    fullname: Nitiss
– volume: 170
  start-page: 507
  year: 2017
  ident: bib12
  article-title: Genome organization drives chromosome fragility
  publication-title: Cell
  doi: 10.1016/j.cell.2017.06.034
  contributor:
    fullname: Canela
– volume: 27
  start-page: 1405
  year: 2017
  ident: bib61
  article-title: Tdp2, top2 And SUMO: What Is ZATT About?
  publication-title: Cell Research
  doi: 10.1038/cr.2017.147
  contributor:
    fullname: Zagnoli-Vieiral
– volume: 13
  start-page: 3202
  year: 2014
  ident: bib24
  article-title: Proteasome inhibitors suppress the protein expression of mutant p53
  publication-title: Cell Cycle
  doi: 10.4161/15384101.2014.950132
  contributor:
    fullname: Halasi
– volume: 59
  start-page: 2121
  year: 2018
  ident: bib19
  article-title: Bortezomib in combination with dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) induces long-term survival in patients with plasmablastic lymphoma: a retrospective analysis
  publication-title: Leukemia & Lymphoma
  doi: 10.1080/10428194.2017.1416365
  contributor:
    fullname: Dittus
– volume: 153
  start-page: 1266
  year: 2013
  ident: bib10
  article-title: 53bp1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions
  publication-title: Cell
  doi: 10.1016/j.cell.2013.05.023
  contributor:
    fullname: Callen
– volume: 9
  start-page: 338
  year: 2009
  ident: bib47
  article-title: Targeting DNA topoisomerase II in Cancer chemotherapy
  publication-title: Nature Reviews Cancer
  doi: 10.1038/nrc2607
  contributor:
    fullname: Nitiss
– volume: 64
  start-page: 580
  year: 2016
  ident: bib25
  article-title: Mre11 is essential for the removal of lethal topoisomerase 2 covalent cleavage complexes
  publication-title: Molecular Cell
  doi: 10.1016/j.molcel.2016.10.011
  contributor:
    fullname: Hoa
– volume: 1
  start-page: 863
  year: 2012
  ident: bib34
  article-title: MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA
  publication-title: Biology Open
  doi: 10.1242/bio.20121834
  contributor:
    fullname: Lee
– volume: 2010
  year: 2010
  ident: bib57
  article-title: Role of topoisomerase iiβ in DNA damage response following IR and etoposide
  publication-title: Journal of Nucleic Acids
  doi: 10.4061/2010/710589
  contributor:
    fullname: Sunter
– volume: 14
  start-page: 417
  year: 2017
  ident: bib41
  article-title: Proteasome inhibitors in cancer therapy
  publication-title: Nature Reviews Clinical Oncology
  doi: 10.1038/nrclinonc.2016.206
  contributor:
    fullname: Manasanch
– volume: 27
  start-page: 2513
  year: 2013
  ident: bib64
  article-title: Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements
  publication-title: Genes & Development
  doi: 10.1101/gad.229559.113
  contributor:
    fullname: Zhang
– volume: 9
  start-page: 2075
  year: 2012
  ident: bib17
  article-title: Mechanism of generation of therapy related leukemia in response to anti-topoisomerase II agents
  publication-title: International Journal of Environmental Research and Public Health
  doi: 10.3390/ijerph9062075
  contributor:
    fullname: Cowell
– volume: 14
  start-page: 1276
  year: 2000
  ident: bib1
  article-title: Protease inhibitor-induced apoptosis: accumulation of wt p53, p21WAF1/CIP1, and induction of apoptosis are independent markers of proteasome inhibition
  publication-title: Leukemia
  doi: 10.1038/sj.leu.2401812
  contributor:
    fullname: An
– volume: 296
  start-page: 922
  year: 2002
  ident: bib14
  article-title: Genomic instability in mice lacking histone H2AX
  publication-title: Science
  doi: 10.1126/science.1069398
  contributor:
    fullname: Celeste
– volume: 103
  start-page: 29
  year: 2016
  ident: bib35
  article-title: Proteasomal inhibition potentiates drugs targeting DNA topoisomerase II
  publication-title: Biochemical Pharmacology
  doi: 10.1016/j.bcp.2015.12.015
  contributor:
    fullname: Lee
– volume: 75
  start-page: 252
  year: 2019
  ident: bib13
  article-title: Topoisomerase II-Induced chromosome breakage and translocation is determined by chromosome architecture and transcriptional activity
  publication-title: Molecular Cell
  doi: 10.1016/j.molcel.2019.04.030
  contributor:
    fullname: Canela
– volume: 264
  start-page: 9713
  year: 1989
  ident: bib26
  article-title: Evidence for the reversibility of cellular DNA lesion induced by mammalian topoisomerase II poisons
  publication-title: The Journal of Biological Chemistry
  doi: 10.1016/S0021-9258(18)81711-2
  contributor:
    fullname: Hsiang
– volume: 281
  start-page: 35997
  year: 2006
  ident: bib62
  article-title: A protease pathway for the repair of topoisomerase II-DNA covalent complexes
  publication-title: Journal of Biological Chemistry
  doi: 10.1074/jbc.M604149200
  contributor:
    fullname: Zhang
– volume: 26
  start-page: 841
  year: 2010
  ident: bib51
  article-title: BEDTools: a flexible suite of utilities for comparing genomic features
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btq033
  contributor:
    fullname: Quinlan
– volume: 10
  year: 2019
  ident: bib21
  article-title: A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome
  publication-title: Nature Communications
  doi: 10.1038/s41467-019-12802-5
  contributor:
    fullname: Gittens
– volume: 461
  start-page: 674
  year: 2009
  ident: bib33
  article-title: A human 5′-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage
  publication-title: Nature
  doi: 10.1038/nature08444
  contributor:
    fullname: Ledesma
– start-page: 481
  volume-title: Methods in Enzymology
  year: 2005
  ident: bib7
  doi: 10.1016/S0076-6879(05)99033-2
  contributor:
    fullname: Bence
– volume: 283
  start-page: 21074
  year: 2008
  ident: bib38
  article-title: A ubiquitin-proteasome pathway for the repair of topoisomerase I-DNA covalent complexes
  publication-title: Journal of Biological Chemistry
  doi: 10.1074/jbc.M803493200
  contributor:
    fullname: Lin
– volume: 63
  start-page: 898
  year: 2016
  ident: bib11
  article-title: DNA Breaks and End Resection Measured Genome-wide by End Sequencing
  publication-title: Molecular Cell
  doi: 10.1016/j.molcel.2016.06.034
  contributor:
    fullname: Canela
– volume: 15
  start-page: 13111
  year: 2014
  ident: bib4
  article-title: DNA break mapping reveals topoisomerase II activity genome-wide
  publication-title: International Journal of Molecular Sciences
  doi: 10.3390/ijms150713111
  contributor:
    fullname: Baranello
– volume: 17
  start-page: 703
  year: 2016
  ident: bib50
  article-title: Roles of eukaryotic topoisomerases in transcription, replication and genomic stability
  publication-title: Nature Reviews Molecular Cell Biology
  doi: 10.1038/nrm.2016.111
  contributor:
    fullname: Pommier
– volume: 10
  year: 2009
  ident: bib31
  article-title: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
  publication-title: Genome Biology
  doi: 10.1186/gb-2009-10-3-r25
  contributor:
    fullname: Langmead
– volume: 152
  start-page: 620
  year: 2013
  ident: bib5
  article-title: Identification of early replicating fragile sites that contribute to genome instability
  publication-title: Cell
  doi: 10.1016/j.cell.2013.01.006
  contributor:
    fullname: Barlow
SSID ssj0000748819
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Snippet Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein...
SourceID doaj
pubmedcentral
proquest
gale
crossref
pubmed
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
SubjectTerms Animal experimentation
Animals
Cancer
Cancer cells
Cell cycle
Cell viability
Chemotherapy
Combination drug therapy
Deoxyribonucleic acid
DNA
DNA - metabolism
DNA Damage
DNA Repair
DNA topoisomerase (ATP-hydrolysing)
DNA Topoisomerases, Type II - metabolism
Double-strand break repair
Drugs
Enzymes
Etoposide
Genetic research
Genetics and Genomics
Genome - genetics
genome instability
Genomes
Genomic instability
Genomics
Health aspects
Humans
Identity
Lymphocytes B
Mice, Inbred C57BL
Proteasome Endopeptidase Complex - metabolism
Proteasome inhibitors
Proteins
Proteolysis
Spleen
Stress management
topoisomerases
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Title Suppressing proteasome mediated processing of topoisomerase II DNA-protein complexes preserves genome integrity
URI https://www.ncbi.nlm.nih.gov/pubmed/32057297
https://www.proquest.com/docview/2384744927
https://www.proquest.com/docview/2355944072
https://pubmed.ncbi.nlm.nih.gov/PMC7089766
https://doaj.org/article/8a1a45021ea14674ad0b85037a8dfae9
Volume 9
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