The Repair of a clustered DNA damage site is influenced by the surrounding DNA lesions

Takahashi, Momoko; Shikazono, Naoya

DNA is damaged by various factors and unrepaired DNA damage would cause alterations of the genome, and various biological effects. Clustered DNA damage, defined as two or more lesions in one to two helical turns of DNA, is induced by ionizing radiation. Clustered DNA damage is considered to be refractory to repair, highly lethal and mutagenic. However, how the clustering of DNA lesions causes mutation is still unknown. Here we represent that surrounding DNA lesions could influence the mutation frequency of a clustered DNA damage site in E. coli. The mutation frequency of clustered DNA damage (GAP/8-oxoG) did not change when another clustered DNA damage (8-oxoG/8-oxoG) was 20 bps away from GAP/8-oxoG. However, when a single 8-oxoG was inserted halfway between the two clusters, the mutation frequency of GAP/8-oxoG was increased. We suggest that the type, the position and the number of DNA lesions influence the efficiency of DNA repair of a clustered DNA damage site.