Error-prone DNA polymerases serve an important function in the cell, due to their unique ability to copy mutagenically past lesions that would normally halt the replication machinery. For this reason it is not surprising that these polymerases are conserved in all three domains of life. In humans these polymerases are important in preventing a rare sunlight-induced cancer known as xeroderma pigmentosum and for the process of somatic hypermutation. The mechanism of translesion synthesis (TLS) is best understood in E. coli, where it involves DNA polymerase V (pol V). Pol V-catalyzed TLS utilizes the single-stranded DNA binding protein (SSB), the replication processivity factor beta-clamp, and requires the RecA protein. Recent data suggest that this requirement is fulfilled by a non-filamentous form of RecA protein, and that RecA may be acting in two modes: one which stimulates pol V, and the other which stimulates TLS. I propose to study the mechanism of targeting pol V to a DNA lesion by studying its interaction with the beta-clamp, RecA, and SSB, and to extend these studies into investigating a """"""""switch"""""""" mechanism between the replicative polymerase, pol llI, and pol V. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM067294-01
Application #
6583681
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Wolfe, Paul B
Project Start
2003-03-01
Project End
2003-11-30
Budget Start
2003-03-01
Budget End
2003-11-30
Support Year
1
Fiscal Year
2003
Total Cost
$32,581
Indirect Cost
Name
University of Southern California
Department
Biochemistry
Type
Other Domestic Higher Education
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089