The non-canonical role of Aurora-A in DNA replication

被引：6
|
作者：
Tsunematsu, Takaaki [1 ]
Arakaki, Rieko [1 ]
Yamada, Akiko [1 ]
Ishimaru, Naozumi [1 ]
Kudo, Yasusei [1 ]
机构：
[1] Univ Tokushima, Grad Sch, Inst Biomed Sci, Dept Oral Mol Pathol, 3-18-15 Kuramoto, Tokushima, Tokushima 7708504, Japan
来源：
FRONTIERS IN ONCOLOGY | 2015年 / 5卷
关键词：
Aurora-A; geminin; DNA replication; pre-RC; ubiquitin; proteasome; degradation; ANAPHASE-PROMOTING COMPLEX; CYCLE-DEPENDENT REGULATION; CELL-CYCLE; UBIQUITIN LIGASE; D-BOX; CENTROSOME AMPLIFICATION; SPINDLE CHECKPOINT; DESTRUCTION BOX; PROTEIN-KINASE; LARGE SUBUNIT;
D O I：
10.3389/fonc.2015.00187
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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/cyclosomemediated 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 gem inin, 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.
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页数：7
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