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- W1567155700 abstract "This dissertation is focused on the functional characterization ofNCOA4 protein, and in particular on its role in controlling DNA replication inHeLa cells.In human papillary thyroid carcinoma the rearrangement of RETprotooncogene, in particular of its tyrosine kinase domain, with the 5’ portionof a number of heterologous genes, generates the RET/papillary thyroidcarcinoma (PTC) oncogenes. One of the most frequent and aggressive variantsof these recombination events is the fusion of the intracellular kinase-encodingdomain of RET to the first 238 amino acids of a gene named NCOA4(ELE1/ARA70/RFG), generating the RET/PTC3 oncogene.We previously isolated the Mini-Chromosome Maintenance 7 (MCM7) proteinas an interactor of NCOA4.MCM7 is a component of an heteroexameric complex named MCM2-7,considered a master regulator of DNA replication, acting both during DNAreplication origins licensing, as part of the Pre-Replication Complex (Pre-RC),and during nascent strand elongation, as the major helicase of the fork. InXenopus laevis egg extracts NCOA4 blocks DNA replication. Hindrance ofDNA replication is mediated by block of MCM2-7 helicase function, leavinguntouched origin licensing and activation.Here we show that NCOA4 and MCM7 proteins interact at theendogenous level in HeLa cells and this interaction is confined in the nucleusand takes place preferentially on chromatin.Moreover, in HeLa cells, NCOA4 binds canonical DNA replication origins,such as those prospicient to the c-Myc or to the Lamin B2 gene.RNAi-mediated depletion of NCOA4 accelerates the onset of DNA replication,whereas adoptive NCOA4 overexpression decreases cell growth and DNAsynthesis.Our results suggest that NCOA4/RET rearrangement might represent anovel paradigm of a cancer-associated chromosome rearrangement that directlytargets a gene that controls cell proliferation." @default.
- W1567155700 created "2016-06-24" @default.
- W1567155700 creator A5018749859 @default.
- W1567155700 date "2009-01-01" @default.
- W1567155700 modified "2023-09-23" @default.
- W1567155700 title "Control of DNA replication by NCOA4 protein in HeLa cells" @default.
- W1567155700 doi "https://doi.org/10.6092/unina/fedoa/3134" @default.
- W1567155700 hasPublicationYear "2009" @default.
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