Sabrina's Post Doc Publications
Irreversible APCCdh1 inactivation underlies the point of no return for cell-cycle entry (Cell 2016)
Proliferating cellsmust cross a point of no return before they replicate their DNA and divide. This commitment decision plays a fundamental role in cancer and degenerative diseases and has been proposed to be mediated by phosphorylation ofretinoblastoma(Rb) protein. Here, we show that inactivation of the anaphase-promoting complex/cyclosome (APCCdh1) has the necessary characteristics to be the point of no return for cell-cycle entry. Our study shows that APCCdh1inactivation is a rapid, bistable switch initi...
p53 suppresses muscle differentiation at the myogenin step in response to genotoxic stress (Cell Death & Differentiation 2015)
Acute muscle injury and physiological stress from chronic muscle diseases and aging lead to impairment of skeletal muscle function. This raises the question of whether p53, a cellular stress sensor, regulates muscle tissue repair under stress conditions. By investigating muscle differentiation in the presence of genotoxic stress, we discovered that p53 binds directly to the myogenin promoter and represses transcription of myogenin, a member of the MyoD family of transcription factors that plays a critical r...
Basal p21 controls population heterogeneity in cycling and quiescent cell cycle states (PNAS 2014)
Phenotypic heterogeneity within a population of genetically identical cells is emerging as a common theme in multiple biological systems, including human cell biology and cancer. Using live-cell imaging, flow cytometry, and kinetic modeling, we showed that two states—quiescence and cell cycling—can coexist within an isogenic population of human cells and resulted from low basal expression levels of p21, a Cyclin-dependent kinase (CDK) inhibitor (CKI). We attribute the p21-dependent heterogeneity in cell cyc...
The Proliferation-Quiescence Decision Is Controlled by a Bifurcation in CDK2 Activity at Mitotic Exit (Cell 2013)
Tissuehomeostasisin metazoans is regulated by transitions of cells between quiescence and proliferation. The hallmark of proliferating populations is progression through the cell cycle, which is driven bycyclin-dependent kinase(CDK) activity. Here, we introduce a live-cell sensor for CDK2 activity and unexpectedly found thatproliferating cellsbifurcate into two populations as they exit mitosis. Many cells immediately commit to the next cell cycle by building up CDK2 activity from an intermediate level, whil...
