The eukaryotic nuclear processes such as replication, DNA damage repair (DDR) and transcription are highly dependent on the regulation of chromatin structure. The dynamic changes in chromatin accessibility are controlled by a class of chromatin-remodeling factors which form multimeric complexes and use ATP as the source of their helicase activity. In this study we have established a mouse embryonic fibroblast in vitro model with conditional inactivation of chromatin remodeling ATPase Smarca5 and used this powerful tool to test the regulation of cell cycle, proliferation and DDR signaling in conditions with low Smarca5 activity. Our results show that decreased dosages lead to decreased proliferation apparent already within few days post induction of Smarca5 deletion that is accompanied with decrease of cells in S and M phases of cell cycle, increasing cell ploidy and accelerated cell senescence. Additionally, the Smarca5 depleted cells upregulated many protein markers associated with DNA damage and cellular stress. Our results thus indicate that Smarca5 has indispensable roles during cell proliferation including in the maintenance of genome integrity during S phase of cell cycle.
| Identifer | oai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:380355 |
| Date | January 2018 |
| Creators | Tauchmanová, Petra |
| Contributors | Stopka, Tomáš, Burda, Pavel |
| Source Sets | Czech ETDs |
| Language | Czech |
| Detected Language | English |
| Type | info:eu-repo/semantics/masterThesis |
| Rights | info:eu-repo/semantics/restrictedAccess |
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