Extrachromosomal DNA in Genome (in)Stability – Role of Telomeres

Eukaryotic genome consists of long linear chromosomes. It is complex in its content and has dynamic features. It mostly consists of non-coding DNA of various repeats, often prone to recombination including creation of extrachromosomal DNA which can be re-integrated into distant parts of the genome, often in different chromosome. These events are usually part of normal genome function enabling molecular response to changes in the cell or organism’s environment and enabling their evolutionary development as well. These mechanisms also contribute to genome instability as in the case of abnormal immortalization like in cancer cells. Telomeres are among most important repetitive sequences, located at the end of linear chromosomes. They serve as guardians of genome stability but they also have dynamic features playing important role in cell aging and immortalization, both as chromosomal components or as extrachromosomal DNA. Also, recombination events on telomeres provide plausible explanation for stochastic nature of cell senescence, a phenomenon unjustly overlooked in broader literature

Humani kromosom 1 u mišjim imortalnim stanicama

Telomeres are specialized structures at the ends of linear chromosomes and are essential for normal cellular function. Telomeres prevent degradation and aberrant recombination of chromosome termini and facilitate appropriate replication of chromosome ends. In this work, the telomere dynamics was followed in the immortal mouse cell strain A9 in comparison with A9+1. The latter is derived from A9 cells by introduction of human chromosome 1. In spite of the telomerase presence, a great decrease in telomere lengths was noticed in A9+1 compared to A9 cells. Behavior of individual human and mouse telomeres was also followed under the conditions of the observed gross telomere shortening. Human chromosome 1 followed the overall telomere length in hybrid cells. It is suggested that telomere lengths are primarily determined by the cell protein background.Telomere su specijalizirane strukture na krajevima linearnih kromosoma i esencijalne su za normalnu staničnu funkciju. One sprečavaju degradaciju i pogrešnu rekombinaciju krajeva kromosoma i olakšavaju replikaciju kromosomskih krajeva. U ovom radu praćena je dinamika telomera u imortalnim mišjim staničnim linijama A9 i A9+1. A9+1 stanična linija dobivena je unošenjem ljudskoga kromosoma 1 u A9 stanice. Usprkos prisustvu telomeraze primijećeno je veliko skraćenje telomera kod A9+1 u usporedbi s A9 stanicama. Praćeno je i ponašanje ljudskoga kromosoma 1 u mišjim stanicama u uvjetima pod kojima je došlo do skraćivanja telomera. Raspon duljina telomera ljudskoga kromosoma 1 odgovarao je rasponu mišjih telomera stanica doma- ćina. Ovi rezultati ukazuju da na raspon duljina telomera najveći utjecaj ima ukupan sastav telomernih proteina stanice

Telomere Q-PNA-FISH - Reliable Results from Stochastic Signals

Structural and functional analysis of telomeres is very important for understanding basic biological functions such as genome stability, cell growth control, senescence and aging. Recently, serious concerns have been raised regarding the reliability of current telomere measurement methods such as Southern blot and quantitative polymerase chain reaction. Since telomere length is associated with age related pathologies, including cardiovascular disease and cancer, both at the individual and population level, accurate interpretation of measured results is a necessity. The telomere Q-PNA-FISH technique has been widely used in these studies as well as in commercial analysis for the general population. A hallmark of telomere Q-PNA-FISH is the wide variation among telomere signals which has a major impact on obtained results. In the present study we introduce a specific mathematical and statistical analysis of sister telomere signals during cell culture senescence which enabled us to identify high regularity in their variations. This phenomenon explains the reproducibility of results observed in numerous telomere studies when the Q-PNA-FISH technique is used. In addition, we discuss the molecular mechanisms which probably underlie the observed telomere behavior

Lifestyle, telomeres and aging – what is the connection?

Telomere shortening is the mayor contributor of cellular aging and telomere length is reliable biomarker of aging process, both at individual as well as at the population level. Short telomeres are also connected with aging related diseases like cancer, cardiovascular diseases and diabetes which are the leading causes of death in the world today. Recently, it has been demonstrated, for the first time, that comprehensive lifestyle changes can slow aging process at molecular level. Such changes include food rich in fiber, fruits and vegetables as well as low fat and low refined carbohydrates diet. If this diet is combined with moderate exercise and stress management techniques, it can result in increased telomerase activity in peripheral mononuclear blood cells during three months period only, which subsequently slow down telomere loss in humans

Polimorfizmi gena FTO na raskrižju metaboličkih puteva pretilosti i epigenetskih utjecaja

In this review, we summarize the current state of knowledge on the fat mass and obesity-associated (FTO) gene and its role in obesity. The FTO-encoded protein is involved in multiple molecular pathways contributing to obesity as well as other metabolic complexities. This review emphasizes the epigenetic influence on the FTO gene as a new approach in the treatment and management of obesity. Several known substances have a positive effect on reducing FTO expression. Depending on which variant of the single nucleotide polymorphism (SNP) is present, the profile and level of gene expression changes. Implementation of environmental change measures could lead to reduced phenotypic manifestation of FTO expression. Treating obesity through FTO gene regulation will have to include various complex signal pathways in which FTO takes part. Identification of FTO gene polymorphisms may be useful for the development of individual obesity management strategies, including the recommendation of taking certain foods and supplements.U ovom preglednom radu sažete su trenutne spoznaje o genu FTO (engl. fat mass and obesity-associated gene) i njegovoj ulozi u razvoju pretilosti. Protein kodiran genom FTO je uključen u razne molekularne puteve koji pridonose pretilosti i drugim metaboličkim poremećajima. Ovaj rad naglašava epigenetski utjecaj gena FTO kao novog pristupa u liječenju pretilosti. Nekoliko poznatih tvari ima pozitivan utjecaj na redukciju ekspresije gena FTO. Ovisno o tome koja je varijanta jednostrukog nukleotidnog polimorfizma (engl. single nucleotide polymorphism, SNP) prisutna, mijenja se profil i razina ekspresije gena. Promjenom uvjeta okoliša može se smanjiti fenotipsko ispoljavanje ekspresije gena FTO. U liječenje pretilosti regulacijom gena FTO treba uključiti različite složene signalne puteve u kojima sudjeluje i sam gen. Identifikacija polimorfizama gena FTO može biti korisna za razvoj individualnih strategija upravljanja pretilošću, uključujući donošenje preporuka za konzumiranje određenih namirnica i suplemenata

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Telomere kontroliraju stanično starenje

It has been well established that various mammalian cells demonstrate a limited growth capacity in culture referred to as cellular or replicative senescence. There is also some evidence in support of the idea that this is the basis for organismal aging. Recent studies have revealed the molecular mechanisms of telomere involvement in cell senescence, cell cycle control, genome (in)stability and immortalization. This has provided an explanation of various phenomena related to process of aging and carcinogenesis. In this review we aim to describe some of the most important features of normal cell aging and the that result in malignant transformation.Dobro je poznato da razni stanični tipovi sisavaca imaju ograničen rast kad se uzgajaju u kulturi, što nazivamo staničnim starenjem. Brojni dokazi upućuju na to da je takav ograničen stanični rast osnova procesa starenja. Nedavna otkrića pokazala su da su telomere ključne za navedene procese i za kontrolu staničnog ciklusa, (ne)stabilnosti genoma i imortalizaciju. U ovom pregledu bit će riječi o telomerama koje su pružile objašnjenja za razne fenomene procesa starenja i karcinogeneze