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.
Froniers in Oncology
Frontiers Media S.A.
Copyright © 2015 Tsunematsu, Arakaki, Yamada, Ishimaru and Kudo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publica- tion in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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