Assembly of nuclear matrix–bound protein complexes involved in non-homologous end joining is induced by inhibition of DNA topoisomerase II

2006 ◽  
Vol 207 (3) ◽  
pp. 660-667 ◽  
Author(s):  
Omar L. Kantidze ◽  
Olga V. Iarovaia ◽  
Sergey V. Razin
Keyword(s):  
Nuclear Matrix ◽  
Topoisomerase Ii ◽  
Protein Complexes ◽  
Dna Topoisomerase Ii ◽  
End Joining ◽  
Dna Topoisomerase ◽  
Matrix Bound ◽  
Non Homologous End Joining

scholarly journals Canonical non-homologous end-joining promotes genome mutagenesis and translocations induced by transcription-associated DNA topoisomerase 2 activity

2020 ◽  
Vol 48 (16) ◽  
pp. 9147-9160
Author(s):  
Joaquín Olmedo-Pelayo ◽  
Diana Rubio-Contreras ◽  
Fernando Gómez-Herreros
Keyword(s):  
Cell Death ◽  
Topoisomerase Ii ◽  
Genome Instability ◽  
Metabolic Enzyme ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Dna Topoisomerase ◽  
Transient Complex ◽  
Topoisomerase 2 ◽  
Non Homologous End Joining

Abstract DNA topoisomerase II (TOP2) is a major DNA metabolic enzyme, with important roles in replication, transcription, chromosome segregation and spatial organisation of the genome. TOP2 is the target of a class of anticancer drugs that poison the DNA-TOP2 transient complex to generate TOP2-linked DNA double-strand breaks (DSBs). The accumulation of DSBs kills tumour cells but can also result in genome instability. The way in which topoisomerase activity contributes to transcription remains unclear. In this work we have investigated how transcription contributes to TOP2-dependent DSB formation, genome instability and cell death. Our results demonstrate that gene transcription is an important source of abortive TOP2 activity. However, transcription does not contribute significantly to apoptosis or cell death promoted by TOP2-induced DSBs. On the contrary: transcription-dependent breaks greatly contribute to deleterious mutations and translocations, and can promote oncogenic rearrangements. Importantly, we show that TOP2-induced genome instability is mediated by mutagenic canonical non-homologous end joining whereas homologous recombination protects cells against these insults. Collectively, these results uncover mechanisms behind deleterious effects of TOP2 abortive activity during transcription, with relevant implications for chemotherapy.

A method for the purification of DNA/protein complexes applied to DNA topoisomerase II cleavage sites

1991 ◽  
Vol 193 (1) ◽  
pp. 101-111 ◽  
Author(s):  
R.J. Anderson ◽  
C. Delgado ◽  
D. Fisher ◽  
J.M. Cunningham ◽  
G.E. Francis
Keyword(s):  
Topoisomerase Ii ◽  
Protein Complexes ◽  
Cleavage Sites ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase

The in vivo distribution and dynamics of DNA topoisomerase II in Drosophila embryonic nuclei and chromosomes

1993 ◽  
Vol 51 ◽  
pp. 74-75
Author(s):  
Jason R. Swedlow ◽  
Neil Osheroff ◽  
Tim Karr ◽  
John W. Sedat ◽  
David A. Agard
Keyword(s):  
Topoisomerase Ii ◽  
Biochemical Characterization ◽  
Developmental Cycle ◽  
Dna Topoisomerase Ii ◽  
Chromosomal Distribution ◽  
Dna Topoisomerase ◽  
Ideal System ◽  
Dnase Treatment

DNA topoisomerase II is an ATP-dependent double-stranded DNA strand-passing enzyme that is necessary for full condensation of chromosomes and for complete segregation of sister chromatids at mitosis in vivo and in vitro. Biochemical characterization of chromosomes or nuclei after extraction with high-salt or detergents and DNAse treatment showed that topoisomerase II was a major component of this remnant, termed the chromosome scaffold. The scaffold has been hypothesized to be the structural backbone of the chromosome, so the localization of topoisomerase II to die scaffold suggested that the enzyme might play a structural role in the chromosome. However, topoisomerase II has not been studied in nuclei or chromosomes in vivo. We have monitored the chromosomal distribution of topoisomerase II in vivo during mitosis in the Drosophila embryo. This embryo forms a multi-nucleated syncytial blastoderm early in its developmental cycle. During this time, the embryonic nuclei synchronously progress through 13 mitotic cycles, so this is an ideal system to follow nuclear and chromosomal dynamics.

DNA Topoisomerase II Enzymes as Molecular Targets for Cancer Chemotherapy

2010 ◽  
Vol 999 (999) ◽  
pp. 1-14 ◽  
Author(s):  
K. Chikamori ◽  
A.G. Grozav ◽  
T. Kozuki ◽  
D. Grabowski ◽  
R. Ganapathi ◽  
...  
Keyword(s):  
Cancer Chemotherapy ◽  
Topoisomerase Ii ◽  
Molecular Targets ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase
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