Topoisomerase IIβ associates with Ku70 and PARP-1 during double strand break repair of DNA in neurons

Mandraju, Rajakumar; Chekuri, Anil; Bhaskar, C.; Duning, Kerstin; Kremerskothen, Joachim; Kondapi, Anand K.

doi:10.1016/j.abb.2011.10.001

Cited by 18 publications

(14 citation statements)

References 43 publications

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“…Several other host cell DNA proteins have been shown associated with the DNA-PK complex ( Fig. 4) such as the already mentioned ATM and ATR but also HDAC4, PARP1 and TOP2B [79]. Of note, it has been shown by immunoprecipitation that Ku70 is associated with TOP2B and PARP1.…”

Section: Dna Repair and Transcriptionmentioning

confidence: 83%

“…TOP2B is a type II DNA topoisomerase which is involved in various cell processes including DNA repair and transcription. Interestingly, HIV-1 subverts TOP2B during the course of reverse transcription and transcription of the HIV-1 life cycle [79,80]. Indeed, overexpression of TOP2B leads to the increase of viral transcription and replication [81].…”

Section: Dna Repair and Transcriptionmentioning

confidence: 99%

“…One mechanism underlying this effect is the facilitation of transcription by the association of TOP2B, Ku70 and PARP1 with the viral transactivator Tat on the HIV-1 LTR promoter. TOP2B also plays a role in the regulation of the transcription of several genes by associating with DNA repair proteins such Ku70 and PARP1 [79,80]. Due to its role of topoisomerase, TOP2B might reorganize the chromatin architecture when associated to DNA damage and DNA repair proteins such as Ku70 and PARP1.…”

Section: Dna Repair and Transcriptionmentioning

confidence: 99%

See 2 more Smart Citations

Targeting the DNA-PK complex: Its rationale use in cancer and HIV-1 infection

Schwartz

Rohr

Wallet

2019

Biochemical Pharmacology

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Section: Dna Repair and Transcriptionmentioning

confidence: 83%

Section: Dna Repair and Transcriptionmentioning

confidence: 99%

Section: Dna Repair and Transcriptionmentioning

confidence: 99%

See 1 more Smart Citation

Targeting the DNA-PK complex: Its rationale use in cancer and HIV-1 infection

Schwartz

Rohr

Wallet

2019

Biochemical Pharmacology

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“…54 Nuclear hormones such as androgen and retinoic acid 24,54,55 have been reported to involve in Topo-2β-mediated transcription. 49 The molecular activities could be delivered through direct interaction of Topo-2β with repair proteins, stabilizing the repair complex or/and the presence of Topo-2β in the repair complex, which may result in the torsional integrity of DNA during the repair, unwinding and rewinding of the DNA without torsional strain. 49 The molecular activities could be delivered through direct interaction of Topo-2β with repair proteins, stabilizing the repair complex or/and the presence of Topo-2β in the repair complex, which may result in the torsional integrity of DNA during the repair, unwinding and rewinding of the DNA without torsional strain.…”

Section: Discussionmentioning

confidence: 99%

Status of topoisomerase‐2β protein in all‐trans retinoic acid–treated human neuroblastoma (SK‐N‐SH) cells

Bhanothu

Kondapi

2018

J of Cellular Biochemistry

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Of the mammalian topoisomerase (Topo)‐2 isozymes (α and β), Topo‐2β protein has been reported to regulate neuronal development and differentiation. However, the status of Topo‐2β in all‐trans retinoic acid (ATRA)‐treated human neuroblastoma (SK‐N‐SH) cells is not understood. More information about the effects of ATRA on SK‐N‐SH cells is needed to reveal the role of ATRA in the regulation of Topo‐2β levels and spontaneous regression of SK‐N‐SH cells to predict the clinical activity. This study was proposed to investigate the status and role of Topo‐2β protein in ATRA‐induced survival and neuronal differentiation of SK‐N‐SH cells. Microscopic, sodium dodecyl sulfate polyacrylamide gel electrophoresis after immunoprecipitations and Western blot analysis were used to study and compare Topo‐2β protein among 10 µM ATRA‐treated SK‐N‐SH cells and controls at different time points. The level of Topo‐2β protein increased in the initial days of treatment but markedly decreased upon induction of differentiation by ATRA in later stages. Upon ATRA treatment, SK‐N‐SH cells stretched, exhibited neurite extensions, and acquired a neuronal phenotype. Both treated and untreated SK‐N‐SH cells were able to migrate, occupy the scratched area, and completely recolonized 24 hours later. These results suggest an indirect role of Topo‐2β protein in regulation of genes involved in cell migration and differentiation of ATRA‐treated SK‐N‐SH cells. This study suggests that Topo‐2β may be part of activation/repression of protein complexes activated by epigenetic modifying agents, differentiating signals, and inducible locus. However, detailed studies are needed to explore the ATRA‐downstream genes leading to Topo‐2β regulation and regulatory proteins of neuronal differentiation.

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“…Considering this importance of ROS and DNA damage, we have studied their levels in in-vitro VM neuronal culture. As topoisomerase II β plays an important role in DNA repair, neuronal development, differentiation, and longevity [5,7,[18][19][20], expression of topoisomerase II β was monitored during the VM neuronal culture in vitro.…”

Section: Introductionmentioning

confidence: 99%

Enriched rat primary ventral mesencephalic neurons as an in-vitro culture model

Bollimpelli

Kondapi

2015

NeuroReport

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Primary ventral mesencephalic (VM) neuronal cultures are gaining importance in the study of molecular mechanisms leading to Parkinson's disease and development of treatment strategies. In practice, these neurons are cocultured with glial cells, making assessment of neuronal specific proteomic and genomic analyses difficult. Hence, development of VM neuron-enriched culture is indispensable for such analyses. In the current study, VM neurons with less than 5% of glial cells in culture were found to survive for 9 days in vitro (DIV), followed by a sudden death phase resulting in less than 5% of neuronal viability. Analysis of expression of precursor and mature neuronal markers, Nestin and MAP-2, respectively, has shown that these VM neurons attain maturity at the 7th DIV both in the presence and in the absence of glial cells. This VM neuron-enriched culture was shown to be rich in dopaminergic neurons from 7th DIV and survived up to 10th DIV. Reactive oxygen species and DNA damage estimated using CMH2CDFDA dye and comet assay, respectively, showed an increase in their respective levels at 9th DIV. Furthermore, expression of topoisomerase II β, a key player in neuronal development, was found to increase until 9th DIV, followed by a sudden decrease on 10th DIV. In conclusion, the above results provide a good working model of VM neurons in vitro along with 7th DIV as an ideal time period to study and evaluate the pro/antisurvival effects of various compounds on VM neurons.

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Topoisomerase IIβ associates with Ku70 and PARP-1 during double strand break repair of DNA in neurons

Cited by 18 publications

References 43 publications

Targeting the DNA-PK complex: Its rationale use in cancer and HIV-1 infection

Targeting the DNA-PK complex: Its rationale use in cancer and HIV-1 infection

Status of topoisomerase‐2β protein in all‐trans retinoic acid–treated human neuroblastoma (SK‐N‐SH) cells

Enriched rat primary ventral mesencephalic neurons as an in-vitro culture model

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