The mitotic kinase, Aurora-A (Aur-A), is important for accurate chromosome segregation. AurA is amplified or over expressed in most of the common cancers. Experimentally, forced over-expression of Aur-A results in aneuploidy, cellular transformation, and tumor formation in mice. New evidence suggests overexpression of Aur-A may override a DNA damage-induced G2 checkpoint arrest. Xenopus egg cycling extracts, which carry out many cell cycle events in vitro, are a convenient and powerful system to investigate the roles of Aur-A in DNA damage checkpoint control. In the proposed work, I will first determine the exact timing of AurA activation in relation to cdc2 activation and the G2tM transition in cycling extracts. I will then ask if DNA damage checkpoints, which block activation of cdc2, also inhibit Aur-A activation. If so, I will determine if this inhibition depends on p53. I will lastly test how the over-expression of AurA may override checkpoint arrest in mammalian somatic cells. These experiments will address the potential important role of Aur- A in proceeding into mitosis under both normal and checkpoint-arrested cell cycle. Studying the potential role of Aur-A in DNA damage checkpoint should provide new insights for understanding the underlying mechanisms for both tumorigenesis and resistance to DNA damage chemotherapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM071101-01
Application #
6783780
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Tompkins, Laurie
Project Start
2004-03-01
Project End
2007-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$54,352
Indirect Cost
Name
Harvard University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115