A5060494193- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Bone and Dental Protein Studies
- Genomics and Chromatin Dynamics
- Sirtuins and Resveratrol in Medicine
- DNA and Nucleic Acid Chemistry
- Calcium signaling and nucleotide metabolism
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- PARP inhibition in cancer therapy
- Adenosine and Purinergic Signaling
- RNA regulation and disease
- Proteoglycans and glycosaminoglycans research
- Metabolomics and Mass Spectrometry Studies
- Stress Responses and Cortisol
- RNA Interference and Gene Delivery
- Evolution and Paleontology Studies
- Neuroscience and Neuropharmacology Research
- Fibroblast Growth Factor Research
- Plant Genetic and Mutation Studies
- Adipose Tissue and Metabolism
University of Rochester
2019-2023
Institute of Cytology
2007-2018
Saint Petersburg State Pediatric Medical University
2015-2017
S. M. Kirov Military Medical Academy
2017
Russian Academy of Sciences
2006-2011
Abstract A sequence variant of histone H2A called H2AX is one the key components chromatin involved in DNA damage response induced by different genotoxic stresses. Phosphorylated (γH2AX) rapidly concentrated domains around double-strand breaks (DSBs) after action ionizing radiation or chemical agents and at stalled replication forks during stress. γH2AX foci could be easily detected cell nuclei using immunofluorescence microscopy that allows to use as a quantitative marker DSBs various...
Abstract Naked mole-rat (NMR), the longest-living rodent, produces very-high-molecular-mass hyaluronan (vHMM-HA), compared to other mammalian species. However, it is unclear if exceptional polymer length of vHMM-HA important for longevity. Here, we show that (>6.1 MDa) has superior cytoprotective properties shorter HMM-HA. It protects not only NMR cells, but also mouse and human cells from stress-induced cell-cycle arrest cell death in a length-dependent manner. The effect dependent on...
Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated aging metabolism regulation. Targeted sequencing of SIRT6 locus population 450 Ashkenazi Jewish (AJ) centenarians 550 AJ individuals without family history exceptional longevity identified enrichment allele containing two linked substitutions (N308K/A313S) compared with control individuals. Characterization this (centSIRT6) demonstrated it to be stronger...
DNA mutations in somatic cells have been implicated the causation of aging, with longer-lived species having a higher capacity to maintain genome sequence integrity than shorter-lived species. In an attempt directly test this hypothesis, we used single-cell whole-genome sequencing analyze spontaneous and bleomycin-induced lung fibroblasts four rodent distinct maximum life spans, including mouse, guinea pig, blind mole-rat, naked as well humans. As predicted, mutagen-induced mutation...
Abstract At over 200 years, the maximum lifespan of bowhead whale exceeds that all other mammals. The is also second-largest animal on Earth, reaching 80,000 kg 1 . Despite its very large number cells and long lifespan, not highly cancer-prone, an incongruity termed Peto’s Paradox 2 This phenomenon has been explained by evolution additional tumor suppressor genes in larger animals, supported research elephants demonstrating expansion p53 gene 3–5 Here we show fibroblasts undergo oncogenic...
When transcribed DNA is damaged, the transcription and repair machineries must interact to ensure successful repair.The mechanisms of this interaction in context chromatin are still being elucidated.Here we show that SIRT6 protein enhances non-homologous end joining (NHEJ) by transiently repressing transcription.Specifically, mono-ADP ribosylates lysine demethylase JHDM1A/KDM2A leading rapid displacement KDM2A from chromatin, resulting increased H3K36me2 levels.Furthermore, found through...
SIRT6 is a protein deacylase, deacetylase, and mono-ADP-ribosylase (mADPr) regulating biological pathways important for longevity including DNA repair silencing of LINE1 retrotransposons. knockout mice die by 30 days age, whereas overexpression increases lifespan in male mice. Finding safe pharmacological activators would have clinical benefits. Fucoidan, polysaccharide purified from brown seaweed, has been identified as an activator deacetylation activity. Here, we show that fucoidan also...
Abstract Calorie restriction (CR) improves health, reduces cancer incidence and extends lifespan in multiple organisms including mice. CR was shown to enhance base excision repair nucleotide pathways of DNA repair, however, whether double-strand breaks has not been examined vivo system. Here we utilize non-homologous end joining (NHEJ) reporter mice show that short-term strongly enhances by NHEJ, which is associated with elevated levels DNA-PK SIRT6.
Studies of DNA damage response are critical for the comprehensive understanding age-related changes in cells, tissues and organisms. Syrian hamster cells halt proliferation become presenescent after several passages standard conditions cultivation due to what is known as «culture stress». Using proliferating young non-dividing primary cultures fibroblasts, we defined their action radiomimetic drug bleomycin (BL) that induces double-strand breaks (DSBs). The effect was estimated by...
Forskolin is a natural compound found in the coleus herb that activates enzyme adenylate cyclase and increases concentration of intracellular cyclic AMP (cAMP). This chemical widely used as stimulating food additive. It unknown whether forskolin can effect cellular responses to ionizing radiation, such induction phosphorylation histone H2AX (gamma-H2AX) megabase chromatin domains near DNA double-strand breaks (DSBs). Here we report treatment with decreases after irradiation detected by...
Abstract Cells continually degrade and replace damaged old proteins. However, the high energetic demand of protein turnover generates reactive oxygen species (ROS) that compromise long-term health proteome. Thus, relationship between aging, remains unclear. Here, we used a proteomic approach to measure rates within primary fibroblasts isolated from number with diverse lifespans including longest-lives rodent, naked mole rat longest-lived mammal, bowhead whale. We show organismal lifespan is...
Abstract Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, naked mole-rat 1, 2 . To study whether benefits HMW-HA could be transferred other animal species, we generated a transgenic mouse overexpressing synthase gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels several tissues, lower incidence spontaneous induced cancer, extended lifespan improved healthspan. The transcriptome...