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Review
. 2015 Aug 25:5:187.
doi: 10.3389/fonc.2015.00187. eCollection 2015.

The Non-Canonical Role of Aurora-A in DNA Replication

Takaaki Tsunematsu  1 , Rieko Arakaki  1 , Akiko Yamada  1 , Naozumi Ishimaru  1 , Yasusei Kudo  1
Affiliations
Review

The Non-Canonical Role of Aurora-A in DNA Replication

Takaaki Tsunematsu et al. Front Oncol. .

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.

Keywords: Aurora-A; DNA replication; degradation; geminin; pre-RC; proteasome; ubiquitin.

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Figures

Figure 1
Figure 1
Relationships between the protein levels of Aurora-A and geminin and anaphase-promoting complex/cyclosome (APC/C) activity during cell cycle progression. The graph shows APC/CCdc20 and APC/CCdh1 activities and the protein levels of Aurora-A and geminin during cell cycle progression.
Figure 2
Figure 2
Schematic model of DNA replication via the aurora-A–geminin–CDT1 axis.
See this image and copyright information in PMC

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