Plyusnina

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THE INFLUENCE OF THE ACTIVITY OF DNA DAMAGE RECOGNITION
AND REPAIR GENES ON THE LIFESPAN OF DROSOPHILA
MELANOGASTER
E.N. Plyusnina1,2, M.V. Shaposhnikov1,2, L.A. Shilova1, A.A. Moskalev1-4
Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar,
2
Syktyvkar State University, Syktyvkar
3
Moscow Institute of Physics and Technology, Dolgoprudny
4
Engelhardt Institute of Molecular Biology, RAS, Moscow, Russia
1
The ability to appropriately respond to environmental and physiological stresses
influences on vitality and longevity of organisms. Stress factors both directly and
indirectly lead to DNA damage, which is a critical event for cell and organism. Key
cellular mechanisms that resist against their action and provide genome integrity are
DNA damage recognition and DNA repair. The aim of this work was to study the role
of genes involved in DNA damage response regulation (Drosophila homologous of
HUS1, ATR, ATM, CHK2, p53, GADD45 genes), DNA excision repair (homologous of
PCNA, XPC, XPF, APE1 genes), and double-strand break repair (homologous of
BRCA2, KU80, WRNexo, XRCC3, RAD54, BLM genes) in the determination of aging
and longevity. To study their action on lifespan and aging rate we applied two
approaches. Firstly, we analyzed the lifespan changes in Drosophila melanogaster flies
with mutations in DNA damage recognition and repair genes, and showed the negative
effect of loss-of-function of these genes. An alternative approach is based on the
investigation of lifespan changes of flies with ectopic activation of studied genes. We
used transgenic flies with both ubiquitous and tissue-specific overexpression of DNA
damage recognition and repair genes by GAL4/UAS system. However, in the most
cases overactivation of DNA repair genes led to lifespan decrease. Reasons of this
adverse effect can include insufficient epigenetic regulation, superfluous energetic
expenses and enhanced aging-related hyperfunction of cellular and organism systems.
This work was supported by the Russian Science Foundation grant N 14-50-00060.
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