The G2/M checkpoint pathway of fission yeast arrests cell cycle progression in the presence of DNA damage and unreplicated DNA. The Rad3 kinase plays a critical role in signaling this cell cycle arrest. Genotoxic insults go unrecognized when rad3+ is mutated, and cells attempt to segregate an abnormal genome. In humans, faulty checkpoint control underlies the symptoms of a disease called Ataxia telangiectasia (A-T). The protein mutated in this disease is ATMp, structurally related to Rad3p. A-T patients suffer from a variety of severe symptoms, including a high incidence of cancers, particularly leukemia and lymphomas. Like rad3 cells, A-T cells are acutely sensitive to ionizing radiation and fail to arrest cell cycle progression in the presence of DNA damage. Rad3p and ATMp are PI-3 related kinases. The regulation of this new family of kinases is not well understood. Evidence suggest they become activated following recruitment by specific protein/DNA complexes.
The specific aim of this research is to understand the mechanisms regulating Rad3p kinase activity in the G2/M checkpoint pathway of fission yeast. Regulation of Rad3p likely occurs through its association with a protein/DNA complex. This hypothesis will be tested using genetic and biochemical techniques to identify and define this protein complex and test if it associates with DNA.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM019773-01
Application #
2767553
Study Section
Biological Sciences 2 (BIOL)
Project Start
1999-04-01
Project End
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115