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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F20%3A73612683" target="_blank" >RIV/61989592:15110/20:73612683 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41467-020-18549-8" target="_blank" >https://www.nature.com/articles/s41467-020-18549-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-020-18549-8" target="_blank" >10.1038/s41467-020-18549-8</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

—

Volume of the periodical

11

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

"nestránkováno"

UT code for WoS article

000573732600003

EID of the result in the Scopus database

2-s2.0-85091179549