3P-B 016
Grappa, a new longevity regulator in Drosophila? °List O.1 , T anaka M.1 , Umeda Y.1,3 , T ogawa T .2 , Matsuo T .1 , Aigaki T .1 1) Dept. Biol. Sci., Tokyo Metropolitan Univ. 2) Dept. Cell. Biol., Univ. Georgia 3) Dept. Ger. Med., Univ. Tokyo Hospital, contact:
[email protected] Introduction
The fruit fly, Drosophila melanogaster, is an excellent model system for the study of complex biological processes including aging and longevity determination. Oxidative stress has been considered to promote aging and shorten the lifespan. In support of this, overexpression of genes encoding antioxidant enzymes, such as superoxide dismutase (SOD) and catalase extended longevity of flies. In order to identify genes that can confer oxidative stress resistance, we have conducted a g ene misexpression screen using P[GS]-insertion lines. Screening of 2 ,7 71 P[GS] lines and the subsequent molecular mapping of the insertion sites identified 17 candidates genes, whose misexpression increases the survival time o f flies kept in media containing 1 % hydrogen peroxide. Among these, we characterized the gene grappa, which encodes a protein with a sequence homology to yeast Dot1, a h istone methyltransferase that modifies the lysine (K)79 residue of histone H3. Recently, it has been shown that grappa is involved in a Polycomb-group-mediated silencing mechanism necessary for the maintenance phase of Bithorax complex expression. In this study, we present how grappa gene influences oxidative stress resistance and longevity in Drosophila using loss-of-function mutations as well as its overexpression.
Overexpression of grappa extends survival period under oxidative stress
Screening using the gene search system
B
A
**
Survival rate(%)
Survival time (hrs)
GS13895
Control Time (hrs)
Control
**
Survival time (hrs)
Survival time (hrs)
**
GS13895
E
D
GS17621
Control
* GS9042
Survival time (hrs)
C
GS10630
Control
GS9042
We examined the oxidative stress resistance of the h s-GAL4/G S (yellow) compared to the control strains (blue lines). The experimen ts were carried out at 30 °C with 3 repetitions for each GS line. (A) Survival curve for one repetition of GS13895 at 30 °C, 1% H 2 O 2 n =32. (B, C, D) h s-GAL4 /G S line o verexpressing g rappa showed a lifespan extension in oxidative stress conditions (1%H 2 O 2 ) compared to the contr ol h s-GAL4/y w. GS10630: +16%; GS13895: +19%; GS17621: +13% (Two ways ANOVA tests, **p
