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The source of endogenous DNA damage in neurodegenerative disease
Havelková, Jarmila ; Hanzlíková, Hana (advisor) ; Vodička, Pavel (referee)
DNA single-strand breaks (SSBs) are amongst the most frequent DNA lesions arising in cells and can threaten genetic integrity and cell survival, as indicated by the elevated genetic deletion, embryonic lethality and neurological disease observed when single-strand break repair (SSBR) is attenuated. One of the proteins important for rapid repair of SSBs is XRCC1, which is a molecular scaffold protein that interacts with multiple DNA repair enzymes (e.g. PARP1, PNKP, POLβ, APTX, LIG3) and thus, promotes their stability and/or function. Defects in SSBR have been associated with hereditary neurodegeneration in humans, cerebellar ataxias and seizures. Here, I focus on genetic disease spinocerebellar ataxia autosomal recessive-26 (SCAR26), which has been shown to be linked to mutations in XRCC1. I investigate the amount of XRCC1 protein in XRCC1-defective cells and reveal that cells from patients with mutations in XRCC1 exhibit greatly reduced XRCC1 levels. I show that reduced levels of XRCC1 protein in cells correlate with the increasing number of endogenous SSBs, measured by quantification of ADP-ribose in the chromatin. In addition, I confirm that the most endogenous SSBs arise in S phase of the cells cycle during replication. Moreover, I prove that the main sources of the endogenous SSBs in...
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The source of endogenous DNA damage in neurodegenerative disease
Havelková, Jarmila ; Hanzlíková, Hana (advisor) ; Vodička, Pavel (referee)
DNA single-strand breaks (SSBs) are amongst the most frequent DNA lesions arising in cells and can threaten genetic integrity and cell survival, as indicated by the elevated genetic deletion, embryonic lethality and neurological disease observed when single-strand break repair (SSBR) is attenuated. One of the proteins important for rapid repair of SSBs is XRCC1, which is a molecular scaffold protein that interacts with multiple DNA repair enzymes (e.g. PARP1, PNKP, POLβ, APTX, LIG3) and thus, promotes their stability and/or function. Defects in SSBR have been associated with hereditary neurodegeneration in humans, cerebellar ataxias and seizures. Here, I focus on genetic disease spinocerebellar ataxia autosomal recessive-26 (SCAR26), which has been shown to be linked to mutations in XRCC1. I investigate the amount of XRCC1 protein in XRCC1-defective cells and reveal that cells from patients with mutations in XRCC1 exhibit greatly reduced XRCC1 levels. I show that reduced levels of XRCC1 protein in cells correlate with the increasing number of endogenous SSBs, measured by quantification of ADP-ribose in the chromatin. In addition, I confirm that the most endogenous SSBs arise in S phase of the cells cycle during replication. Moreover, I prove that the main sources of the endogenous SSBs in...
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Sleep related neurohumoral regulation of weight management
Havelková, Jarmila ; Tomešová, Jitka (advisor) ; Suchánek, Pavel (referee)
Over the past three decades, it has been confirmed that the alarming increase in number of obese patients is related to the sleep duration and its quality. Neurohumoral response to short sleep duration and poor sleep quality leads to decreased levels of melatonin, leptin and orexin, asto increased levels of cortisol, ghrelin and neuropeptide Y. Such an inaccurate regulation contributes both to excessive intake of energy-dense diet and to the reduction of energy expenditure during physical activity. The bachelor thesis summarizes recent information about the relationship of sleep and obesity, focusing on hormones and peptides involved in the regulation of energy balance processes, including the posssibility to use their mechanisms for weight control.
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