A stable genome is critical to cell viability and proliferation. During DNA replication, the S-phase checkpoint pathway responds to replication stress. In budding yeast, the chromatin-bound F-box protein Dia2 is required to maintain genomic stability and may help replication complexes overcome sites of damaged DNA and natural fragile regions. SCF (Skp1/Cul1/F-box protein) complexes are modular ubiquitin ligases. We show here that Dia2 is itself targeted for ubiquitin-mediated proteolysis and that activation of the S-phase checkpoint pathway inhibits Dia2 protein degradation. S-phase checkpoint mutants fail to stabilize Dia2 in response to replication stress. Deletion of DIA2 from these checkpoint mutants exacerbates their sensitivity to hydroxyurea, suggesting that stabilization of Dia2 contributes to the replication stress response. Unlike the case for other F-box proteins, deletion of the F-box domain in Dia2 does not stabilize the protein. Rather, an N-terminal domain that is also required for nuclear localization is necessary for degradation. When a strong nuclear localization signal (NLS) is added to dia2 mutants lacking this domain, the Dia2 protein is both stable and nuclear. Together, our results suggest that Dia2 protein turnover does not involve an autocatalytic mechanism and that Dia2 proteolysis is inhibited by activation of the replication stress response.
We show that the five possible ordered states in a quantum spin-1/2 system
With long-range exchange interactions: Neel, ladder, Peierls, coincidence, and
Domain states, can be realized in a binary Rydberg-dressed BEC system in the
Supersolid phase. In such a system, blockade phenomenon is shown to a...
We present both chip-scale and free space coherent arrays of continuous-wave
THz photomixers. By altering the relative phases of the exciting laser signals,
The relative THz phase between the array elements can be tuned, allowing for
Beam steering. The constructive interference of the emission of N...
We present extensive Monte Carlo simulations on a two-dimensional XY model
With a modified form of interaction potential. Thermodynamic quantities other
Than energy, specific heat etc (such as magnetization, susceptibility, fourth
Order cumulant of magnetization) are obtained using multiple-histogra...
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