Ribosome biogenesis is one of the most fundamental of cellular processes because without ribosomes cells cease growing. In metazoan cells, ribosome biogenesis is cell cycle regulated, as both transcription and processing of ribosomes ceases during mitosis (Dundr, 1998; Sirri, 2000). Currently, little else known about the connection between ribosome biogenesis and the cell cycle. Using yeast as a model system, first I plan to determine whether ribosome biogenesis is cell cycle regulated. Second, I will determine whetheNanl/Utpl 7 may provide a regulatory link between these two processes. Nanl/Utpl7, Net 1 associated nucleolarprotein, was originally purified as a component of the RENT complex, Regulator of Nuclealor Silencing and Telophase, which is important for mitotic exit (Shou, 1999). It has also been purified as a component of the newly purified SSU processome, where it affects processing of 18S ribosomal subunits (Dragon et al., Submitted). Therefore, Nanl/Utpl7 may provide a link between these two processes. Finally, I will determine whether there are a critical number of ribosomes needed for growth and division. In studying the link between these two fundamental processes, I will be able to understand how abnormal cell growth and ribosome synthesis are directly connected, such as in the case of human cancers.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM067564-02
Application #
6659915
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Rene, Anthony
Project Start
2002-09-16
Project End
2005-09-15
Budget Start
2003-09-16
Budget End
2004-09-15
Support Year
2
Fiscal Year
2003
Total Cost
$39,117
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Bernstein, Kara A; Bleichert, Franziska; Bean, James M et al. (2007) Ribosome biogenesis is sensed at the Start cell cycle checkpoint. Mol Biol Cell 18:953-64
Bernstein, Kara A; Granneman, Sander; Lee, Alicia V et al. (2006) Comprehensive mutational analysis of yeast DEXD/H box RNA helicases involved in large ribosomal subunit biogenesis. Mol Cell Biol 26:1195-208
Bernstein, Kara A; Gallagher, Jennifer E G; Mitchell, Brianna M et al. (2004) The small-subunit processome is a ribosome assembly intermediate. Eukaryot Cell 3:1619-26
Bernstein, Kara A; Baserga, Susan J (2004) The small subunit processome is required for cell cycle progression at G1. Mol Biol Cell 15:5038-46