A. Szakmary et al., OVEREXPRESSION OF A RRP1 TRANSGENE REDUCES THE SOMATIC MUTATION AND RECOMBINATION FREQUENCY INDUCED BY OXIDATIVE DNA-DAMAGE IN DROSOPHILA-MELANOGASTER, Proceedings of the National Academy of Sciences of the United Statesof America, 93(4), 1996, pp. 1607-1612
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.