SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells. / Obara, Elisabeth Anne Adanma; Aguilar-Morante, Diana; Rasmussen, Rikke Darling; Frias, Alex; Vitting-Serup, Kristoffer; Lim, Yi Chieh; Elbæk, Kirstine Juul; Pedersen, Henriette; Vardouli, Lina; Jensen, Kamilla Ellermann; Skjoth-Rasmussen, Jane; Brennum, Jannick; Tuckova, Lucie; Strauss, Robert; Dinant, Christoffel; Bartek, Jiri; Hamerlik, Petra.

In: Nature Communications, Vol. 11, 4709, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Obara, EAA, Aguilar-Morante, D, Rasmussen, RD, Frias, A, Vitting-Serup, K, Lim, YC, Elbæk, KJ, Pedersen, H, Vardouli, L, Jensen, KE, Skjoth-Rasmussen, J, Brennum, J, Tuckova, L, Strauss, R, Dinant, C, Bartek, J & Hamerlik, P 2020, 'SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells', Nature Communications, vol. 11, 4709. https://doi.org/10.1038/s41467-020-18549-8

APA

Obara, E. A. A., Aguilar-Morante, D., Rasmussen, R. D., Frias, A., Vitting-Serup, K., Lim, Y. C., Elbæk, K. J., Pedersen, H., Vardouli, L., Jensen, K. E., Skjoth-Rasmussen, J., Brennum, J., Tuckova, L., Strauss, R., Dinant, C., Bartek, J., & Hamerlik, P. (2020). SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells. Nature Communications, 11, [4709]. https://doi.org/10.1038/s41467-020-18549-8

Vancouver

Obara EAA, Aguilar-Morante D, Rasmussen RD, Frias A, Vitting-Serup K, Lim YC et al. SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells. Nature Communications. 2020;11. 4709. https://doi.org/10.1038/s41467-020-18549-8

Author

Obara, Elisabeth Anne Adanma ; Aguilar-Morante, Diana ; Rasmussen, Rikke Darling ; Frias, Alex ; Vitting-Serup, Kristoffer ; Lim, Yi Chieh ; Elbæk, Kirstine Juul ; Pedersen, Henriette ; Vardouli, Lina ; Jensen, Kamilla Ellermann ; Skjoth-Rasmussen, Jane ; Brennum, Jannick ; Tuckova, Lucie ; Strauss, Robert ; Dinant, Christoffel ; Bartek, Jiri ; Hamerlik, Petra. / SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells. In: Nature Communications. 2020 ; Vol. 11.

Bibtex

@article{59d5a02299324ffbbcdef57e9dac81ce,
title = "SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells",
abstract = "Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and the accessibility of DNA lesions to DNA repair machineries are crucial for the maintenance of genomic stability. Understanding the functional impact of chromatin remodeling on DNA repair in GSCs may lay the foundation for advancing the efficacy of radio-sensitizing therapies. Here, we present the results of a high-content siRNA microscopy screen, revealing the transcriptional elongation factor SPT6 to be critical for the genomic stability and self-renewal of GSCs. Mechanistically, SPT6 transcriptionally up-regulates BRCA1 and thereby drives an error-free DNA repair in GSCs. SPT6 loss impairs the self-renewal, genomic stability and tumor initiating capacity of GSCs. Collectively, our results provide mechanistic insights into how SPT6 regulates DNA repair and identify SPT6 as a putative therapeutic target in glioblastoma.",
keywords = "Animals, Apoptosis, BRCA1 Protein, Brain Neoplasms/genetics, Cell Cycle Checkpoints, Cell Line, Tumor, DNA Repair, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Gene Silencing, Genomic Instability, Glioblastoma/genetics, HEK293 Cells, Heterografts, Humans, Mice, Mice, Inbred BALB C, Neoplastic Stem Cells/pathology, RNA, Small Interfering/genetics, Radiation Tolerance, Radiation, Ionizing, Transcription Factors/genetics, Transcriptome",
author = "Obara, {Elisabeth Anne Adanma} and Diana Aguilar-Morante and Rasmussen, {Rikke Darling} and Alex Frias and Kristoffer Vitting-Serup and Lim, {Yi Chieh} and Elb{\ae}k, {Kirstine Juul} and Henriette Pedersen and Lina Vardouli and Jensen, {Kamilla Ellermann} and Jane Skjoth-Rasmussen and Jannick Brennum and Lucie Tuckova and Robert Strauss and Christoffel Dinant and Jiri Bartek and Petra Hamerlik",
year = "2020",
doi = "10.1038/s41467-020-18549-8",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells

AU - Obara, Elisabeth Anne Adanma

AU - Aguilar-Morante, Diana

AU - Rasmussen, Rikke Darling

AU - Frias, Alex

AU - Vitting-Serup, Kristoffer

AU - Lim, Yi Chieh

AU - Elbæk, Kirstine Juul

AU - Pedersen, Henriette

AU - Vardouli, Lina

AU - Jensen, Kamilla Ellermann

AU - Skjoth-Rasmussen, Jane

AU - Brennum, Jannick

AU - Tuckova, Lucie

AU - Strauss, Robert

AU - Dinant, Christoffel

AU - Bartek, Jiri

AU - Hamerlik, Petra

PY - 2020

Y1 - 2020

N2 - Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and the accessibility of DNA lesions to DNA repair machineries are crucial for the maintenance of genomic stability. Understanding the functional impact of chromatin remodeling on DNA repair in GSCs may lay the foundation for advancing the efficacy of radio-sensitizing therapies. Here, we present the results of a high-content siRNA microscopy screen, revealing the transcriptional elongation factor SPT6 to be critical for the genomic stability and self-renewal of GSCs. Mechanistically, SPT6 transcriptionally up-regulates BRCA1 and thereby drives an error-free DNA repair in GSCs. SPT6 loss impairs the self-renewal, genomic stability and tumor initiating capacity of GSCs. Collectively, our results provide mechanistic insights into how SPT6 regulates DNA repair and identify SPT6 as a putative therapeutic target in glioblastoma.

AB - Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and the accessibility of DNA lesions to DNA repair machineries are crucial for the maintenance of genomic stability. Understanding the functional impact of chromatin remodeling on DNA repair in GSCs may lay the foundation for advancing the efficacy of radio-sensitizing therapies. Here, we present the results of a high-content siRNA microscopy screen, revealing the transcriptional elongation factor SPT6 to be critical for the genomic stability and self-renewal of GSCs. Mechanistically, SPT6 transcriptionally up-regulates BRCA1 and thereby drives an error-free DNA repair in GSCs. SPT6 loss impairs the self-renewal, genomic stability and tumor initiating capacity of GSCs. Collectively, our results provide mechanistic insights into how SPT6 regulates DNA repair and identify SPT6 as a putative therapeutic target in glioblastoma.

KW - Animals

KW - Apoptosis

KW - BRCA1 Protein

KW - Brain Neoplasms/genetics

KW - Cell Cycle Checkpoints

KW - Cell Line, Tumor

KW - DNA Repair

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Gene Knockdown Techniques

KW - Gene Silencing

KW - Genomic Instability

KW - Glioblastoma/genetics

KW - HEK293 Cells

KW - Heterografts

KW - Humans

KW - Mice

KW - Mice, Inbred BALB C

KW - Neoplastic Stem Cells/pathology

KW - RNA, Small Interfering/genetics

KW - Radiation Tolerance

KW - Radiation, Ionizing

KW - Transcription Factors/genetics

KW - Transcriptome

U2 - 10.1038/s41467-020-18549-8

DO - 10.1038/s41467-020-18549-8

M3 - Journal article

C2 - 32948765

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 4709

ER -

ID: 249528327