Our research is focused on understanding how the cell cycle is regulated and coordinated to maintain faithful genomic integrity. We have studied the regulation of S phase entry, a major checkpoint of cell division, when cells must correctly and with high fidelity initiate DNA replication while preventing re-initiation and re-replication. Misregulation of this transition leads to genomic instability, a hallmark of cancer. We use both mammalian cells and extracts from the frog, Xenopus laevis, to study cyclin-dependent kinase inhibitors, replication factors, ubiquitin ligases, and tumor suppressors that are key regulators of the cell cycle. We strive to understand the roles of these factors in genome maintenance and how to correct the consequences of their aberrant regulation in cancer.
Zhu XN, Kim DH, Lin HR, Budhavarapu VN, Rosenbaum HB, Mueller PR, Yew PR. Proteolysis of Xenopus Cip-type CDK inhibitor, p16Xic2, is regulated by PCNA binding and CDK2 phosphorylation. Cell Div. 2013 Apr 22;8(1):5.
Kim DH, Budhavarapu VN, Herrera CR, Nam HW, Kim YS, Yew PR. The CRL4Cdt2 ubiquitin ligase mediates the proteolysis of cyclin-dependent kinase inhibitor Xic1 through a direct association with PCNA. Mol Cell Biol. 2010 Sep;30(17):4120-33.
Philpott A, Yew PR. The Xenopus cell cycle: an overview. Mol Biotechnol. 2008 May;39(1):9-19.
Lin HR, Chuang LC, Boix-Perales H, Philpott A, Yew PR. Ubiquitination of cyclin-dependent kinase inhibitor, Xic1, is mediated by the Xenopus F-box protein xSkp2. Cell Cycle. 2006 Feb;5(3):304-14.
Chuang LC, Yew PR. Proliferating cell nuclear antigen recruits cyclin-dependent kinase inhibitor Xic1 to DNA and couples its proteolysis to DNA polymerase switching. J Biol Chem. 2005 Oct 21;280(42):35299-309. (Selected as a Journal of Biological Chemistry “Paper of the Week”)