title: Lifespan and Stress Resistance in Drosophila with Overexpressed DNA Repair Genes.
abstract: DNA repair declines with age and correlates with longevity in many animal species. In this study, we investigated the effects of GAL4-induced overexpression of genes implicated in DNA repair on lifespan and resistance to stress factors in Drosophila melanogaster. Stress factors included hyperthermia, oxidative stress, and starvation. Overexpression was either constitutive or conditional and either ubiquitous or tissue-specific (nervous system). Overexpressed genes included those involved in recognition of DNA damage (homologs of HUS1, CHK2), nucleotide and base excision repair (homologs of XPF, XPC and AP-endonuclease-1), and repair of double-stranded DNA breaks (homologs of BRCA2, XRCC3, KU80 and WRNexo). The overexpression of different DNA repair genes led to both positive and negative effects on lifespan and stress resistance. Effects were dependent on GAL4 driver, stage of induction, sex, and role of the gene in the DNA repair process. While the constitutive/neuron-specific and conditional/ubiquitous overexpression of DNA repair genes negatively impacted lifespan and stress resistance, the constitutive/ubiquitous and conditional/neuron-specific overexpression of Hus1, mnk, mei-9, mus210, and WRNexo had beneficial effects. This study demonstrates for the first time the effects of overexpression of these DNA repair genes on both lifespan and stress resistance in D. melanogaster.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.|Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, 167982, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shaposhnikov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.|Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, 167982, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Proshkina
authors.affiliation: Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, 167982, Russia.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Shilova
authors.affiliation: Insilico Medicine, Inc, Johns Hopkins University, ETC, B301, Baltimore, MD, 21218, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Zhavoronkov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Moskalev
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics*; D005260:Female; D005334:Fever / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D018384:Oxidative Stress / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins