The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner
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The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner. / Deville, Sara Sofia; Vehlow, Anne; Förster, Sarah; Dickreuter, Ellen; Borgmann, Kerstin; Cordes, Nils.
In: CANCERS, Vol. 12, No. 7, 28.06.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner
AU - Deville, Sara Sofia
AU - Vehlow, Anne
AU - Förster, Sarah
AU - Dickreuter, Ellen
AU - Borgmann, Kerstin
AU - Cordes, Nils
PY - 2020/6/28
Y1 - 2020/6/28
N2 - The treatment resistance of cancer cells is a multifaceted process in which DNA repair emerged as a potential therapeutic target. DNA repair is predominantly conducted by nuclear events; yet, how extra-nuclear cues impact the DNA damage response is largely unknown. Here, using a high-throughput RNAi-based screen in three-dimensionally-grown cell cultures of head and neck squamous cell carcinoma (HNSCC), we identified novel focal adhesion proteins controlling DNA repair, including the intermediate filament protein, synemin. We demonstrate that synemin critically regulates the DNA damage response by non-homologous end joining repair. Mechanistically, synemin forms a protein complex with DNA-PKcs through its C-terminal tail domain for determining DNA repair processes upstream of this enzyme in an ATM-dependent manner. Our study discovers a critical function of the intermediate filament protein, synemin in the DNA damage response, fundamentally supporting the concept of cytoarchitectural elements as co-regulators of nuclear events.
AB - The treatment resistance of cancer cells is a multifaceted process in which DNA repair emerged as a potential therapeutic target. DNA repair is predominantly conducted by nuclear events; yet, how extra-nuclear cues impact the DNA damage response is largely unknown. Here, using a high-throughput RNAi-based screen in three-dimensionally-grown cell cultures of head and neck squamous cell carcinoma (HNSCC), we identified novel focal adhesion proteins controlling DNA repair, including the intermediate filament protein, synemin. We demonstrate that synemin critically regulates the DNA damage response by non-homologous end joining repair. Mechanistically, synemin forms a protein complex with DNA-PKcs through its C-terminal tail domain for determining DNA repair processes upstream of this enzyme in an ATM-dependent manner. Our study discovers a critical function of the intermediate filament protein, synemin in the DNA damage response, fundamentally supporting the concept of cytoarchitectural elements as co-regulators of nuclear events.
U2 - 10.3390/cancers12071717
DO - 10.3390/cancers12071717
M3 - SCORING: Journal article
C2 - 32605308
VL - 12
JO - CANCERS
JF - CANCERS
SN - 2072-6694
IS - 7
ER -