The long-term goal of this research program is to understand how eukaryotic DMA replication is regulated during the cell cycle. This problem is central to understanding the mechanisms that control cellular proliferation and maintain genomic stability. Our approach to this problem involves the use of genetic and biochemical methods to identify and characterize proteins involved in initiation of DMA replication and its control in the model organism Schizosaccharomyces pombe. Our major objectives are to characterize the assembly and activation of initiation complexes, to define the biochemical mechanisms involved in the replication checkpoint, and to characterize a DNA replication-dependent DMA damage checkpoint that we have recently discovered. We expect that information obtained in our studies will complement that obtained from the study of the Saccharomyces cerevisiae and will be directly relevant to the control of DNA replication in higher eukaryotes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050806-16
Application #
7651328
Study Section
Molecular Genetics A Study Section (MGA)
Program Officer
Santangelo, George M
Project Start
1994-05-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2011-06-30
Support Year
16
Fiscal Year
2009
Total Cost
$441,477
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Callegari, A John; Kelly, Thomas J (2016) Coordination of DNA damage tolerance mechanisms with cell cycle progression in fission yeast. Cell Cycle 15:261-73
Callegari, A John; Clark, Emily; Pneuman, Amanda et al. (2010) Postreplication gaps at UV lesions are signals for checkpoint activation. Proc Natl Acad Sci U S A 107:8219-24
Houchens, Christopher R; Lu, Wenyan; Chuang, Ray-Yuan et al. (2008) Multiple mechanisms contribute to Schizosaccharomyces pombe origin recognition complex-DNA interactions. J Biol Chem 283:30216-24
Dai, Jianli; Chuang, Ray-Yuan; Kelly, Thomas J (2005) DNA replication origins in the Schizosaccharomyces pombe genome. Proc Natl Acad Sci U S A 102:337-42
Brown, G W; Kelly, T J (1999) Cell cycle regulation of Dfp1, an activator of the Hsk1 protein kinase. Proc Natl Acad Sci U S A 96:8443-8
Brown, G W; Kelly, T J (1998) Purification of Hsk1, a minichromosome maintenance protein kinase from fission yeast. J Biol Chem 273:22083-90