proposal): The proposal suggests that RPA, a multisubunit (p70, p34 and p11) protein, which is involved in DNA replication and DNA repair, may be a target for regulation. This stems from the fact that the amount of RPA subunits does not vary during the cell cycle. Hence, the DNA replication and DNA repair activities of RPA could be regulated by either protein assembly or post- translational modification. The investigator proposes to test whether the assembly of the RPA complex is regulated during the cell cycle. In addition, he will examine whether RPA regulates the formation of initiation complexes at the SV40 origin of replication. Since phosphorylation of RPA could have a role in regulating its activities, the investigator will map the phosphorylation sites and will characterize the kinases in this phosphorylation. RPA phosphorylation sites will be mutated and mutant RPA will be analyzed along with the wild type RPA in a coupled repair- replication system, which was recently developed in the investigator's laboratory.
| Pisarev, V M; Lee, S H; Connelly, M C et al. (1997) Intracellular metabolism and action of acyclic nucleoside phosphonates on DNA replication. Mol Pharmacol 52:63-8 |
| Kim, D K; Stigger, E; Lee, S H (1996) Role of the 70-kDa subunit of human replication protein A (I). Single-stranded dna binding activity, but not polymerase stimulatory activity, is required for DNA replication. J Biol Chem 271:15124-9 |
| Park, M S; Ludwig, D L; Stigger, E et al. (1996) Physical interaction between human RAD52 and RPA is required for homologous recombination in mammalian cells. J Biol Chem 271:18996-9000 |
