A cell-cycle stage-related chromosomal X-ray hypersensitivity in larval neuroblast of Drosophila mei-9 and mei-41 mutants suggesting defecting DNA double-strand break repair

Abstract

We have examined the chromosomal X-ray hypersensitivity in relation to the cell cycle in larval neuroblasts of the mutagen-sensitive and excusion repair-defective mutant mei-9 and of the mutagen-sensitive and post-replication repair-defective mutant mei-41 of Drosophila melanogaster. When compared to wild-type cells, cells bearing the mei-9 L1 allele produced unusually high levels in particular of chromatid deletions and to a lesser extent also of isochromatid deletions, but virtually no exchange aberrations. The chromosomal hypersensitivity is apprent at M 1 when cells are irradiated in S or G 2 but not when irradiated in G 1. On the other hand, following irradiation cells bearing the mei-41 D5 allele predominantly produce chromosome deletions. Also dicentric and chromatid exchange formation is enhanced with a moderate increase in chromatid deletions. The phases of major sensitivity are the S and G 1. Mei-9 and mei-41 mutants have been classified to date as proficient in DNA double-strand break repair. The data presented in this paper revealed an S-independent clastogenic hypersensitivity of mei-9 and mei-41 cells. They are interpreted as indicative evidence for the presence of impaired DNA double-strand break repair. The cell-cycle-related difference in the ratio of chromatid-versus chromosome-type deletions in both mutants suggests repair defects at partially different phases of the cell cycle in mei-9 and mei-41 mutant cells.