The catalytic subunits of cellular replicases are distinguished from simpler polymerases by a complex modular structure that permits interaction with a wide array of DNA replication proteins. Using the alpha subunit of bacterial DNA polymerase III holoenzyme as a prototype, we will study the function of these modules and communication between them. We will investigate the sites involved in binding the beta processivity factor and the tau 'organizer' subunit of the DnaX complex, as well as the interplay in affinities that enables recycling during Okazaki fragment synthesis. The binding sites for the epsilon proofreading subunit within alpha will be determined, and the mechanism used to integrate the polymerase and exonuclease active sites will be further explored. We will also determine the function of other conserved domains and motifs found in replicative polymerases. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060273-06
Application #
7281636
Study Section
Molecular Genetics A Study Section (MGA)
Program Officer
Portnoy, Matthew
Project Start
2000-02-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
6
Fiscal Year
2007
Total Cost
$296,592
Indirect Cost
Name
University of Colorado at Boulder
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
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