OVEREXPRESSION OF A RRP1 TRANSGENE REDUCES THE SOMATIC MUTATION AND RECOMBINATION FREQUENCY INDUCED BY OXIDATIVE DNA-DAMAGE IN DROSOPHILA-MELANOGASTER

Recombination repair protein 1 (Rrp1) includes a C-terminal region hom ologous to several DNA repair proteins, including Escherichia coil exo nuclease III and human APE, that repair oxidative and alkylation damag e to DNA, The nuclease activities of Rrp1 include apurinic/apyrimidini c endonuclease, 3'-phosphodiesterase, 3'-phosphatase, and 3'-exonuclea se. As shown previously, the C-terminal nuclease region of Rrp1 is suf ficient to repair oxidative- and alkylation-induced DNA damage in repa ir-deficient E. coli mutants. DNA strand-transfer and single-stranded DNA renaturation activities are associated with the unique N-terminal region of Rrp1, which suggests possible additional functions that incl ude recombinational repair or homologous recombination. By using the D rosophila w/w(+) mosaic eye system, which detects loss of heterozygosi ty as changes in eye pigmentation, somatic mutation and recombination frequencies were determined in transgenic flies overexpressing wild-ty pe Rrp1 protein from a heat-shock-inducible transgene. A large decreas e in mosaic clone frequency is observed when Rrp1 overexpression prece des treatment with gamma-rays, bleomycin, or paraquat, In contrast, Rr p1 overexpression does not alter the spot frequency after treatment wi th the alkylating agents methyl methanesulfonate or methyl nitrosourea . A reduction in mosaic clone frequency depends on the expression of t he Rrp1 transgene and on the nature of the induced DNA damage, These d ata suggest a lesion-specific involvement of Rrp1 in the repair of oxi dative DNA damage.