The broad, long-term objective of the proposed work is to understand the processes by which large (greater than l kilobase) deletions are formed in the genomes of living cells, particularly those induced by spontaneous processes and by ionizing radiations. The approach is to collect and analyze relevant data in the literature. Specific aims are: (1) studies of large deletions of spontaneous origin in mammalian cells; (2) completion of investigation showing that most radiation-induced deletions in mammalian cells are formed by a single lesion; (3) proof of the working hypothesis that large deletions are formed by two processes: one involving only a single lesion, the second loss of DNA between two double-strand breaks; (4) extension of the theory of the collision rate in the cell between the endpoints of a large deletion; (5) collection of data on the relation between deletion endpoints and base sequence; (6) study of relations in loss of heterozygosity between large deletions and recombination (or gene conversion); (7) study of large deletions in bacteria and yeasts.
NIH ExPorter
NIH ExPorter