This laboratory is engaged in the following projects: 1) Nucleotide sequence analysis of DNA. Using a reaction catalyzed by the T4 DNA polymerase we have developed a method for determining 3' terminal sequences of duplex DNA. We have previously applied this method to T7 DNA and lambda DNA, and have identified up to 7 nucleotides at a 3' terminus. In the case of lambda DNA we have discovered that there are symmetrical sequences at the termini. This symmetry may be involved in the formation of the cohesive end of this DNA when it is cut from a concatemer precursor. We are presently investigating the terminal sequences of DNA molecules from phages P2, 299, and 186. These molecules resemble lambda in that they have cohesive ends, and we are interested in finding if their terminal sequences are symmetrical as well. 2) The inhibition of E.coli DNA replication in vivo by cyanide and CO. We are investigating whether the inhibition of replication is due to a reduction in the concentration of ATP. We are using the luciferase assay to measure ATP concentration. We are also investigating the mechanism by which cells recover from cyanide or CO inhibition and we are attempting to identify replicative intermediates which accumulate during cyanide or CO inhibition.