| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
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| Initial Amendment Date: | March 5, 2003 |
| Latest Amendment Date: | February 22, 2007 |
| Award Number: | 0237483 |
| Award Instrument: | Continuing Grant |
| Program Manager: |
Patrick P. Dennis
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | March 1, 2003 |
| End Date: | February 29, 2008 (Estimated) |
| Total Intended Award Amount: | $0.00 |
| Total Awarded Amount to Date: | $402,000.00 |
| Funds Obligated to Date: |
FY 2004 = $120,000.00 FY 2005 = $127,000.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
701 East Pratt St., Suite 200 Baltimore MD US 21202-3101 (410)385-6330 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
9600 Gudelsky Drive Rockville MD US 20850-3479 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): |
INSTRUMENTAT & INSTRUMENT DEVP, Genetic Mechanisms |
| Primary Program Source: |
app-0104 app-0105 |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
Every proliferating cell must duplicate its genetic information accurately and only once per cell cycle. Any process that falls short of or exceeds these limits results in cell death or abnormal proliferation. The long-term goal of this research program is to understand the mechanisms governing DNA replication in eukarya, and this research project will focus specifically on the origin of replication, a specific location on the chromosome where replication initiates. Whereas DNA replication has been well characterized in bacteria, viruses and bacteriophages, many aspects of the process in eukarya, particularly in the initiation phase, are still unknown. The complex eukaryotic cell cycle entails numerous regulatory signals and factors from the first step of origin recognition to the final step of cell division, making it difficult to study individual components and events. An organism that may help to circumvent some of the complexity of eukaryotic replication is a prokaryote with eukaryotic-like replication processes,the archaeon Methanothermobacter thermautotrophicus (Mth). Archaeal DNA replication appears to be more similar to the eukaryal rather than the bacterial process. However, the archaeal DNA replication apparatus appears to require fewer proteins and complexes. Thus, archaea may provide a good model system for understanding the enzymology of eukaryotic replication. The research will focus on the mechanisms of the initiation of DNA replication in Mth.Both wild-type and mutant recombinant proteins will be used in in vitro experiments designed to:1) isolate and identify the origin binding proteins,2)
understand how the origin is recognized and bound by the initiation proteins; and 3) identify the functional motifs in the archaeal origin. A long-term goal is to develop an in vitro replication system for Mth; the information gained from these biochemical studies will be directly applicable to such a system.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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