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. ? ?