This proposal is to bring together workers in the areas of DNA replication and mutagenesis for a combined meeting focusing on the events of DNA replication which effect mutagenic events. The area of DNA replication is rapidly advancing with increasing definition of the proteins required for initiation and elongation. At the same time, studies in mutagenesis are becoming defined at the molecular level with accumulation of a large mass of data with regard to the spectra of mutagenesis and the contributions of the host cell to mutagenesis. Recent evidence from several laboratories implicates specific replication events in mutagenesis and recently developed techniques allow the analysis of large numbers of transfecting or chromosomal mutations. It is the intent of this meeting to open new contacts between investigators. This meeting is not part of a continuing series, but has been designed to satisfy a defined need. We anticipate that the meeting will be attended by 200-250 outstanding individuals from around the world. Poster sessions will provide an opportunity for all investigators to present recent work in great detail. Discussion leaders and speakers will be drawn from outstanding members of the research community, but a distinct effort will be made to include junior investigators and those with recent striking findings in the formal presentations. Session chairmen will be such outstanding scientists as Arthur Kornberg (Stanford), Charles Richardson (Harvard Medical School), Thomas Lindahl (ICRF, London), Paul Modrich (Duke University Medical School), Harrison Echols (Berkeley), Jeffrey Miller (UCLA), and Peter Herrlich (Karlsruhe). The sessions will cover: the basic enzymology of DNA replication, including the components of the replicative apparatus; DNA replication systems; including both prokaryotic and eukaryotic studies; mechanisms of misincorporation, including errors by the synthesis apparatus as well as adduct formation; the genetic control of mutagenesis, with particular attention to mismatch repair; DNA polymerase functions in mutagenesis; damage-directed mutagenesis, with attention to the spectrum seen in transfecting and chromosomal genes; and induced mutagenesis, with updating on eukaryotic systems. The impact of this meeting should have long term affects on the research in the areas of DNA replication and damage, DNA repair, mutagenesis, birth defects, toxicology, and cellular regulation of gene expression.
