title: The Non-Canonical Role of Aurora-A in DNA Replication.
abstract: Aurora-A is a well-known mitotic kinase that regulates mitotic entry, spindle formation, and chromosome maturation as a canonical role. During mitosis, Aurora-A protein is stabilized by its phosphorylation at Ser51 via blocking anaphase-promoting complex/cyclosome-mediated proteolysis. Importantly, overexpression and/or hyperactivation of Aurora-A is involved in tumorigenesis via aneuploidy and genomic instability. Recently, the novel function of Aurora-A for DNA replication has been revealed. In mammalian cells, DNA replication is strictly regulated for preventing over-replication. Pre-replication complex (pre-RC) formation is required for DNA replication as an initiation step occurring at the origin of replication. The timing of pre-RC formation depends on the protein level of geminin, which is controlled by the ubiquitin-proteasome pathway. Aurora-A phosphorylates geminin to prevent its ubiquitin-mediated proteolysis at the mitotic phase to ensure proper pre-RC formation and ensuing DNA replication. In this review, we introduce the novel non-canonical role of Aurora-A in DNA replication.
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School , Tokushima , Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tsunematsu
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School , Tokushima , Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Arakaki
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School , Tokushima , Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School , Tokushima , Japan.
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School , Tokushima , Japan.
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
keywords: Aurora-A; DNA replication; degradation; geminin; pre-RC; proteasome; ubiquitin