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Full-Text Articles in Molecular Biology
Functional Investigation Of The Role Of The Retinoblastoma Protein In Genome Stability, Aren E. Marshall
Functional Investigation Of The Role Of The Retinoblastoma Protein In Genome Stability, Aren E. Marshall
Electronic Thesis and Dissertation Repository
Genome instability is an enabling characteristic of cancerous cells. It has recently been discovered that the retinoblastoma protein (pRB), typically known for its role in cell cycle regulation, also aids in the maintenance of genome stability. Intriguingly, mutations to the pRB gene, RB1, can arise late in tumorigenesis in cancer cells whose cell cycle regulation is already compromised by another mutation. This suggests that pRB’s functions in genome stability could underlie cancer relevant characteristics that are independent of its ability to negatively regulate proliferation. The overall aim of this thesis is to characterize the different means through which pRB …
Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites
Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites
Electronic Thesis and Dissertation Repository
Cellular division is primarily controlled at the G1 to S-phase transition of the cell cycle by the retinoblastoma tumor-suppressor protein (pRB). The ability of pRB to restrict S-phase entry is primarily attributed to the repression of E2F transcription factors required to upregulate cell cycle target genes necessary for cellular division. Interestingly, while pRB is disrupted in the vast majority of human cancers, mutations typically target upstream regulators of pRB leading to inactivation through hyperphosphorylation. The rarity of direct pRB mutations suggests that the regulation of the cell cycle by pRB may involve additional mechanisms outside of E2F repression, as this …
The Epigenetic Regulators Atrx And Ctcf Are Required For Mouse Neuroprogenitor Cell Survival And Brain Development, Lauren Ashley Watson
The Epigenetic Regulators Atrx And Ctcf Are Required For Mouse Neuroprogenitor Cell Survival And Brain Development, Lauren Ashley Watson
Electronic Thesis and Dissertation Repository
Emerging evidence implicates the regulation of higher-order chromatin structure in brain development, maturation, and function. Human mutations in two important regulators of chromatin structure, ATRX and CTCF, cause microcephaly and intellectual disability and have been identified in several cancers, suggesting an important role for these proteins in the developing brain and to suppress tumorigenesis. This thesis demonstrates that chromatin structure is critical to the differentiation and survival of neural progenitor cells, and explores the mechanisms of ATRX and CTCF function in brain development. The first chapter identifies that Atrx deficiency induces replicative DNA damage at telomeres and pericentromeric heterochromatin, and …