The intermediate filament synemin regulates non-homologous end joining in an ATM-dependent manner
The intermediate filament synemin regulates non-homologous end joining in an ATM-dependent manner
Deville, S.; Vehlow, A.; Förster, S.; Dickreuter, E.; Borgmann, K.; Cordes, N.
Abstract
Treatment resistance of cancer cells is a multifaceted process in which DNA repair emerged as 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.
Keywords: Synemin; DNA-PKcs; ATM; DNA repair; NHEJ; radiosensitivity; HNSCC
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Cancers 12(2020)7, 1717
DOI: 10.3390/cancers12071717
Cited 11 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-31231