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Open Access Publications from the University of California

Structural and mechanistic insights into the regulation of cellular quiescence by Rb and p130

  • Author(s): Hirschi, Alexander
  • Advisor(s): Rubin, Seth M
  • et al.

The ability of a single cell to grow, replicate its genetic material, and divide into two identical daughter cells is a vital process to ensure the propagation of all life. This process is known as the cell division cycle (cell cycle) and is one of the most highly spatially and temporally regulated cellular processes. Misregulation of the cell cycle, particularly in ways that confer both a proliferative advantage and escape from ultimate growth control mechanisms like cellular senescence or apoptosis, can result in unrestrained cell division and tumor formation. In this study, I utilize structural biology, biochemistry, and biophysical data to demonstrate a novel mechanism regulating Rb phosphorylation state and to map pairwise interactions in a conserved cell-cycle regulatory complex called the MuvB Core. First, competition between CDK and PP1 for Rb access provides an efficient regulatory mechanism to dephosphorylate Rb during mitotic exit and times of genotoxic stress. Second, data is presented mapping domain contacts in the MuvB Core, and structure/function studies with MuvB Core suggest an atypical function in regulation of chromatin structure.

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