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Telomeres protect the ends of chromosomes maintaining genome stability. The activity of telomerase enzyme, or alternatively the process of recombination, regulates the length of telomeres. In the absence of these mechanisms, excessive shortening of telomeres reach its critical level. Excessively shortened telomeres do not protect chromosome ends, the cell division cycle is stopped while the inactivity of replication process generates cellular senescence and cell death. On the other hand, critically shortened telomeres may promote chromosomal instability. These changes can lead to the development of carcinogenesis. In this process enzymatic activity of telomerase is reactivated. To maintain the protection of the chromosome ends, telomeres bind the stabilizing protein complex (shelterin). The presence of these protective proteins prevents undesirable DNA damage and initiates the repair system pathways. Molecular technologies enable the evaluation of telomere lengths, the analysis of telomerase expression and activity, and detection of mutations, polymorphic and epigenetic changes in telomere – shelterin - telomerase complex related genes. The purpose of research is to describe new mechanisms that affect the biology of telomere lengths, and to determine the impact on bone marrow failures, development of haematological malignancies, neurodegenerative diseases and others disorders associated with chromosomal instability. The model of modern therapies based on telomere biology explains the significance of the maintenance of telomere lengths in the process of cellular senescence and carcinogenesis. [ABSTRACT FROM AUTHOR]

Advances in high resolution microscopy techniques and development of high throughput DNA analyses allow to reconsider the views concerning bacterial chromosome (nucleoid). Recent reports show that nucleoid exhibits a hierarchical organization, similarly to the eukaryotic chromatin. However, bacterial chromosome undergoes constant modifications and topological rearrangements due to the ongoing DNA replication, transcription and translation processes. Organization of dynamic and highly compacted nucleoid structure depends on physical factors acting on chromosome molecule inside small cell compartment, and is a consequence of action of many different DNA-binding proteins. The main goal of this review is to present the recent reports on bacterial chromatin structure and to elucidate the physical and molecular factors influencing its intracellular organization.

High replication fidelity, understood as the DNA polymerases’ ability to select nucleotides with both correct base and sugar, is of critical importance for maintaining the genetic stability. Due to the fact that the cellular levels of ribonucleotides are much higher than the concentrations of deoxyribonucleotides, replicative polymerases are able to incorporate ribonucleotides with up to 1000-fold higher frequency than mismatched deoxyribonucleotides. The ability to discriminate against ribonucleotides by the DNA polymerases relies on the steric gate residue in the enzyme’s catalytic centre. Despite the fact that ribonucleotides are the most abundantly inserted incorrect nucleotides in DNA, they are not observed in properly functioning cells. The major pathway responsible for the recognition and removal of ribonucleotides from DNA is called Ribonucleotide Excision Repair. The impairment of ribonucleotide removal pathways can cause increased mutation rate, replication stress, DNA breakage, problems with transcription, chromatin structure maintenance, genetic disorders and cell death. In spite of that, ribonucleotide incorporation into DNA may have some positive biological impact, stimulating mismatch repair and non-homologous end joining.

Primases are responsible for the synthesis of a short oligo RNA, which serves as primer for DNA polymerase. Primases play an essential role in the initiation of DNA replication at the origins, in the synthesis of Okazaki fragments and in the restart of stalled replication forks. Prokaryotic primases based on their structure and sequence alignments are classified as a family of DnaG proteins. Primases from this family contain three distinct domains: an amino terminal domain with a zinc ribbon motif involved in binding template DNA, a middle RNA polymerase domain, and a carboxyl-terminal region that either interacts with a helicase or is itself a DNA helicase. In this review, we are presenting the comparison of the representative primases from bacteria and bacteriophages, their mode of action and their involvement in DNA replication at the replication fork.

About 50 years ago, "magic spots" - mediators of the bacterial stringent response, were discovered and were later identified as guanosine tetra- and pentaphosphate (ppGpp and pppGpp, jointly referred to as (p)ppGpp). At first, it seemed that stringent response is associated only with bacterial response to amino acid starvation, however, it soon turned out that (p)ppGpp is synthesized in response to other stresses as well. The mentioned alarmones are found to exist in all known bacterial species, as well as in plants. In recent years, a significant progress has been made in research on (p)ppGpp metabolism. It is also known that the stringent response affects many cellular processes, among which its effect on transcription is the best characterized. Moreover, (p)ppGpp is involved in the DNA repair pathway associated with transcription. In addition, the stringent response inhibits cell division, mainly by hindering DNA replication. (p)ppGpp is also of significant medical importance - it is necessary for virulence of many bacterial species and for turning them into persisters, i.e. cells which have elevated tolerance to many antibiotics.

We reviewed the literature on the relationship between the Fanconi anemia pathway (FA) and response to chemotherapy in patients with ovarian cancer. Despite continuous developments in medicine, ovarian cancer remains a challenge for both, physicians and researchers seeking ways to achieve better results of chemotherapy combined with other targeted therapies. Clinically relevant resistance to chemotherapy is a major problem in treating ovarian cancer. Researchers continue to investigate mechanisms responsible for drug resistance in order to develop better therapeutic methods against ovarian cancer. Among the resistance mechanisms, defects in DNA repair, including the FA pathway may be important in increasing the sensitivity of ovarian cancer cells to chemotherapy agents at the clinical level. A growing number of data has shown that disruption of the FA genes may be a useful predictor of OC sensitivity to chemotherapy agents whose activity is based on DNA crosslinking mechanisms.

Development of the eukaryotic cell proceeds through sequentional stages of the cell cycle, in which there are growth, replication of the genetic material, and cell division processes. Many environmental and intracellular factor decides if the cell proceeds throughout all stages of the cell cycle or enters the G₀ silencing phase. The cell cycle depends also on metabolic processes, including central carbon metabolism and DNA replication. One cof major processes of the central carbon metabolism is glycolysis. This is the main pathway of glucose metabolism in cells, leading to conversion of this molecule to puryvare. Until recently, it was supposed that carbon metabolism and DNA replication are linked only indirectly, mostly through energy input, necessary for synthesis of nucleic acids, and production of precursors of deoxyribonucleotides. Nevertheless, recent studies, described and discussed in this article, suggested that there are much more complicated links, perhaps also direct, between these two processes.

The Fanconi anemia (FA) pathway is one of the DNA repair systems involved in removal of DNA crosslinks. Proteins which belong to this pathway are crucial to the protection of genetic information, whereas disturbances in their function have serious implications for the whole organism. Biallelic mutations in FA genes are the cause of Fanconi anemia - a genetic disease which manifests itself through numerous congenital abnormalities, chromosomal instability and increased predisposition to cancer. The FA pathway is composed of fifteen proteins. Eight of them, in the presence of DNA interstrand crosslinks (ICLs), form a nuclear core complex responsible for monoubiquitination of FANCD2 and FANCI, which is a key step of ICL repair. FA proteins which are not involved in the monoubiquitination step participate in repair of DNA double strand breaks via homologous recombination. Some of the FA proteins, besides having a direct role in the repair of DNA damage, are engaged in replication, cell cycle control and mitosis. The unperturbed course of those processes determines the maintenance of genome stability.

The MCM (minichromosome maintenance protein) protein family was identified for the first time in budding yeast, Saccharomyces cerevisiae. The subgroup consists of MCM proteins 2-9, that possess the characteristic ATPase domain (MCM box). There are also MCM1 and MCM10, which are important in DNA replication, but they do not possess the specific MCM box. The main function of MCM proteins is cooperation with other factors in molecular mechanisms that form the replication fork and in regulation of DNA synthesis. MCM proteins form a ring-shaped complex, which is activated when other factors are bound. MCM 2-7 complex is one of the pre-replication factors. Association of MCM 2-7 complex is a crucial moment initiating the replication fork. MCM proteins play a role in maintaining genome integrity and prevent re-replication once per cell cycle. Proliferating cells have high levels of MCM, whereas they are not detected in quiescent, differentiated or senescent cells. They are also potential useful markers of cell proliferation. Recent studies suggested that MCMs are good markers of proliferation activity degree, because they are highly expressed in a variety of tumors. The aim of this work is to summarize current knowledge about the role of MCM proteins in DNA replication and potential diagnostic markers of proliferating cancer cells.

The cell nucleus is separated from a cytoplasm by a nuclear envelope (NE) composed of nuclear lamina (NL), outer (ONM) and inner nuclear membrane (INM), connected in the region of nuclear pore complexes (NPC), which are sites for macromolecular transport between the nucleus and the cytoplasm. The nuclear lamina is an essential structure mainly composed of type V intermediate filament proteins, A- and B-type lamins, located between the inner nuclear membrane and the peripheral chromatin. Nuclear envelope, which is composed of integral membrane proteins of the INM (LAP1, LAP2, emerin, MAN1, LBR), has many functions including: connection of nucleoskeleton with cytoskeleton, nuclear lamina meshwork and chromatin. This structure plays a role in maintenance of nuclear shape, spacing of nuclear pore complexes, organization of heterochromatin, DNA replication, and regulation of transcription factors. During cell division NE undergoes depolimerization and reassociation. Latest data suggests, that proteins creating nuclear envelope take part in mitosis.

Influenza viruses represent Orthomyxoviridae family. Spherical virions are 80-120 nm in diameter and have two-layer lipid envelope. The following proteins are coded by 8 or 7 segments of the single-stranded RNA: nucleoprotein (NP), polymerase PB2, PB1 and PA, member protein--M1 and M2, glycoproteins--hemagglutinin (HA) and neuraminidase (NA). HA and NA form spikes on the virion surface. On the basis of antigenic differences there are distinguished three types of influenza virus-A, B and C. Besides, influenza A viruses occur in different subtypes, depending on the features of HA and NA. One of influenza characteristics is its antigenic changeability: antigenic drift and antigenic shift. Infection occurs by droplet route, sometimes through direct contact with infected person or surface. Influenza virus attacks epithelial cells of upper respiratory tract, where replication takes place resulting in the production of approximately 1000 of progeny virions during a single 6-12 h cycle in one cell. Necrosis of ciliary cells of mucosa facilitates invasion of bacterial pathogens. Incubation period lasts on average 1-2 days. Influenza illness without complications characterizes the sudden onset of respiratory symptoms and systemic symptoms. Regression of symptoms usually occurs after 3-5 days, but cough and malaise may be observed for over 2 weeks. Reasons for the severe course of the disease or even death are post-influenza complications, e.g. viral pneumonia and bronchitis, bronchiolitis in children, secondary bacterial pneumonia, otitis media, myocarditis and pericarditis, Reye's syndrome, myositis, myoglobinuria, neurological complications and exacerbation of existing chronic diseases. In the case of influenza there is no possible to make the unquestionable diagnosis only on the basis of clinical picture of the disease. Therefore in some circumstances there is important to make some diagnostic laboratory tests as RT-PCR, immunofluorescence assay or isolation of virus and detection of the specific antibodies. The main determinants of the immunity to influenza virus infection are antihemagglutinin (anti-HA) antibodies and antineuraminidase antibodies (anti-NA). The former play fundamental role for the protection against the infection, while anti-NA antibodies limit virus spreading and contribute to a milder course of the disease. In the response to influenza infection there are observed serum immunoglobulines IgG and IgM (after the first contact with the antigen), while immunoglobulines IgA are produced rarely. The latter are produced locally in the high concentrations on the mucus of respiratory tract. Cellular immunological response is important for recovery from influenza where a significant role of cytotoxic T lymphocytes should be emphasized. These lymphocytes are able to kill infected cells in the earliest phases of replication before the progeny virions are formed.

Knowledge about eukaryotic DNA polymerases has increased considerably during recent years. Much have been learnt about both the structures and the functions of "classical" DNA polymerases alpha, beta, delta, epsilon and gamma. New DNA polymerases that possess very unusual functions have been identified. They are able to perform translesional synthesis, take part in somatic hypermutation and prevent some cancers. Much attention has also been devoted to the role of 3'-->5' exonuclease activity in the accuracy of DNA synthesis. On the other hand, it have been shown that there are also negative aspects of the activity of DNA polymerases. Lack of some DNA polymerases or even their altered functions may lead to carcinogenesis and accelerate the process of ageing.

Helicobacter pylori is a Gram-negative, spiral-shaped pathogenic bacterium that was firstly isolated and cultured from biopsy specimens by Marshall and Warren in 1983. This organism is a human gastric pathogen associated with peptic ulcer disease as well as chronic gastritis. Recent epidemiological studies have demonstrated that H. pylori is a primary risk factor for the development of intestinal type gastric adenocarcinoma. H. pylori is the first bacterium for which the genomes of two unrelated strains (26695 and J99) have been sequenced. The genome of H. pylori is relatively low in size (1.6-1.73 Mb). In this review, we compare the organization of two sequenced H. pylori genomes. A special emphasis on genetic diversity of H. pylori including plasticity zone and cag pathogenicity island has been placed.