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Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2
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Publication Restricted Dissecting the regulation of the centrosome/cilium complex biogenesis using proximity-based proteomics(Koç University, 2022) Arslanhan Gül, Melis Dilara; Karalar, Elif Nur Fırat; 0000-0001-7589-473X; Koç University Graduate School of Sciences and Engineering; Molecular Biology and Genetics; 206349Publication Restricted Elucidation of the mechanisms that underlie centriolar satellite biogenesis and dynamics(Koç University, 2022) Gülensoy, Dila; Karalar, Elif Nur Fırat; 0000-0001-7589-473X; Koç University Graduate School of Sciences and Engineering; Molecular Biology and Genetics; 206349Publication Restricted ENKD1 is a centrosomal and ciliary microtubule-associated protein important for primary cilium content regulation(Koç University, 2021) Yıldız, Fatmanur Tiryaki; Karalar, Elif Nur Fırat; 0000-0001-7589-473X; Koç University Graduate School of Sciences and Engineering; Molecular Biology and Genetics; 206349Publication Restricted Mechanistic dissection of the centriole duplication and ciliogenesis proximity interaction maps(Koç University, 2018) Culfa, Efraim; Karalar, Elif Nur Fırat; 0000-0001-7589-473X; Koç University Graduate School of Sciences and Engineering; Molecular Biology and Genetics; 206349Publication Metadata only Prolonged overexpression of PLK4 leads to formation of centriole rosette clusters that are connected via canonical centrosome linker proteins(Nature Portfolio, 2024) Özcan, Selahattin Can; Kalkan, Batuhan Mert; Çiçek, Enes; Canbaz, Ata Alpay; Ayhan, Ceyda Açılan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of MedicineCentrosome amplification is a hallmark of cancer and PLK4 is one of the responsible factors for cancer associated centrosome amplification. Increased PLK4 levels was also shown to contribute to generation of cells with centriole amplification in mammalian tissues as olfactory neuron progenitor cells. PLK4 overexpression generates centriole rosette (CR) structures which harbor more than two centrioles each. Long term PLK4 overexpression results with centrosome amplification, but the maturation of amplified centrioles in CRs and linking of PLK4 induced amplified centrosomes has not yet been investigated in detail. Here, we show evidence for generation of large clustered centrosomes which have more than 2 centriole rosettes and define these structures as centriole rosette clusters (CRCs) in cells that have high PLK4 levels for 2 consecutive cell cycles. In addition, we show that PLK4 induced CRs follow normal centrosomal maturation processes and generate CRC structures that are inter-connected with canonical centrosomal linker proteins as C-Nap1, Rootletin and Cep68 in the second cell cycle after PLK4 induction. Increased PLK4 levels in cells with C-Nap1 and Rootletin knock-out resulted with distanced CRs and CRCs in interphase, while Nek2 knock-out inhibited separation of CRCs in prometaphase, providing functional evidence for the binding of CRC structures with centrosomal linker proteins. Taken together, these results suggest a cell cycle dependent model for PLK4 induced centrosome amplification which occurs in 2 consecutive cell cycles: (i) CR state in the first cell cycle, and (ii) CRC state in the second cell cycle.