Wyniki wyszukiwania

1

Hydroxylamine and methoxyamine mutagenesis: Tautomeric equilibrium of the promutagenic, N6-methoxyadenosine in solvents of different polarities

100%

Kierdaszuk B., Stolarski R., Shugar D.

Acta Biochimica Polonica

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1984

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tom 31

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nr 1

2

Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways

100%

Kulikowska E., Kierdaszuk B., Shugar D.

Acta Biochimica Polonica

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2004

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tom 51

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nr 2

The 6-oxopurine xanthine (Xan, neutral form 2,6-diketopurine) differs from the corresponding 6-oxopurines guanine (Gua) and hypoxanthine (Hyp) in that, at physiological pH, it consists of a = 1:1 equilibrium mixture of the neutral and monoanionic forms, the latter due to ionization of N(3)-H, in striking contrast to dissociation of the N(1)-H in both Gua and Hyp at higher pH. In xanthosine (Xao) and its nucleotides the xanthine ring is predominantly, or exclusively, a similar monoanion at physiological pH. The foregoing has, somewhat surprisingly, been widely overlooked in studies on the properties of these compounds in various enzyme systems and metabolic pathways, including, amongst others, xanthine oxidase, purine phosphoribosyltrans- ferases, IMP dehydrogenases, purine nucleoside phosphorylases, nucleoside hydro- lases, the enzymes involved in the biosynthesis of caffeine, the development of xanthine nucleotide-directed G proteins, the pharmacological properties of alkyl- xanthines. We here review the acid/base properties of xanthine, its nucleosides and nucleotides, their N-alkyl derivatives and other analogues, and their relevance to studies on the foregoing. Included also is a survey of the pH-dependent helical forms of polyxanthylic acid, poly(X), its ability to form helical complexes with a broad range of other synthetic homopolynucleotides, the base pairing properties of xanthine in synthetic oligonucleotides, and in damaged DNA, as well as enzymes involved in circumventing the existence of xanthine in natural DNA.

3

Chlorophyll-proteins complexes and photochemical activity of mesophyll and bundle sheath chloroplasts of C4 plants

100%

Drozak A., Zwolinska P., Kierdaszuk B., Romanowska E.

Polish Journal of Natural Sciences. Supplement

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2003

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tom 01

4

Transformation of dimeric low-affinity form of human thymidine kinase [TK1] to the tetrameric high-affinity form [ATP-form]

100%

Zuberek J., Munch-Petersen B., Shugar D., Kierdaszuk B.

Cellular and Molecular Biology Letters

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1999

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tom 04

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nr 3

5

Enantiospecificity of human deoxycytidine kinase [dCK] and thymidine kinases [TK1 and TK2] towards 3'-branched homologues of 2'-deoxynucleosides

88%

Banrowski M., Krawiec K., Johansson N. G., Shugar D., Kierdaszuk B.

Cellular and Molecular Biology Letters

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1999

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tom 04

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nr 3

6

Unusual nucleoside triphosphate donors for nucleoside kinases: 3'-deoxyadenosine-2'-triphosphate and 2'-deoxyadenosine-3'-triphosphate

88%

Krawiec K., Kierdaszuk B., Kalinichenko E. N., Mikhailopulo I. A., Shugar D.

Acta Biochimica Polonica

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1998

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tom 45

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nr 1

Two non-conventional analogues of ATP, 3'-deoxyadenosine-2'-triphosphate (3'-d-2'-ATP) and 2'-deoxyadenosine-3'-triphosphate (2'-d-3'-ATP), the syntheses of which are described, were examined as potential phosphate donors for the nucleoside kinases: 2'-deoxycytidine kinase (dCK), cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2). The reactions were monitored by means of a mixture of [γ-32P]ATP and cold analogue, andór with the use of 3H-labelled acceptors and cold donor. With dCK, using equimolar mixtures of ATP with each analogue, and dC as acceptor, phosphate transfer from 3'-d-2'-ATP and 2'-d-3'-ATP amounted to 34% and 14%, respectively. With each analogue used alone (each at concentration of 100 μM), phosphate transfer from 3'-d-2'-ATP was 55% that from ATP, and from 2'-d-3'-ATP 16%. With human TK2, and equimolar mixtures of [γ-32P]ATP with each of the analogues, and 1 μM dT as acceptor, there was no detectable transfer from either analogue. But, when each analogue was used alone, phosphate transfer attained 11% and 5%, respectively, that for ATP alone. With the low affinity form of human TK1, and dT as acceptor, only low phosphate transfer occurred with either analogue used alone. Both compounds exhibited Michaelis-Menten kinetics (with significantly lower Vmax than ATP), while ATP exhibited cooperative kinetics with all three kinases.

7

Chronic progressive external ophthalmoplegia in Polish patients – clinical and genetic characteristics

76%

Kierdaszuk B., Kaliszewska M., Tonska K., Bartnik E., Kaminska A. M., Kostera-Pruszczyk A.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

INTRODUCTION: Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders which may result from mutations in mitochondrial (mtDNA) and nuclear genome (nDNA). From a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. AIM(S): The aim of this study was the clinical and genetic characteristics of Polish patients with progressive external ophthalmoplegia. METHOD(S): Clinical, electrophysiological, neuroradiological and morphological data of 45 patients aged 11 to 76 years were analyzed. Genetic studies of mtDNA were performed in all patients. Among nDNA genes POLG was studied in 15 and C10orf2 in 6 patients. RESULTS: 16 patients with ptosis and PEO were included to chronic progressive external ophthalmoplegia (CPEO) group and 13 with ptosis, PEO and limb or trunk muscles’ weakness to CPEO+ group. There were 11 patients with PEO and the central nervous system impairment classified as mitochondrial encephalomyopathy (ME), 4 patients with Kearns-Sayre syndrome (KSS) and one patient with sensory ataxic neuropathy, dysarthria, ophthalmoparesis (SANDO) syndrome. Genetic studies of mtDNA revealed already known single or multiple mtDNA deletions in all patients and in most cases they were detected in the muscle tissue. Genetic analysis of nDNA genes confirmed mutations in POLG gene in 6 patients. There were 3 CPEO patients with p.[Arg309Leu];[Gln968Glu], p.[Ala518Thr];[=] and p.[Trp748Ser];[Ser998Pro] mutations, and 2 CPEO+ patients with p.[Thr251Ile;Pro587Leu];[Thr251Ile;Pro587Leu] and p.[Thr251Ile;Pro587Leu];[Lys1191Asn] mutations. In patient with SANDO syndrome the mutation p.[Arg290Cys];[Arg309Cys] in POLG gene was confirmed. Additionally the analysis of the C10orf2 gene proved the mutation p.[Arg374Gln];[=] in one CPEO patient CONCLUSIONS: Genetic studies of both mtDNA and nDNA are necessary for diagnosis of chronic progressive external ophthalmoplegia and its genetic counseling.

8

Genetics of mitochondrial diseases – from mitochondrial DNA to whole exome studies

64%

Tonska K., Kaliszewska M., Rusecka J., Kierdaszuk B., Rydzanicz M., Stawinski P., Ploski R., Kaminska A.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

Mitochondrial diseases, caused by dysfunction of the respiratory chain are characterised by very high clinical as well as genetic heterogeneity. In most of the cases multiple organs and systems are involved with special place taken by muscular and nervous systems due to their high respiratory requirements. From the genetic point of view mitochondrial diseases are exceptionally difficult to study. As the respiratory chain function is secured by the cooperation of up to 1500 proteins, the number of genes in which mutations may lead to OXPHOS dysfunction may be close to that number. Another difficulty is that the respiratory chain subunits are encoded by two different genomes. 13 of them are localised in mitochondrial DNA (mtDNA) – small, multicopy maternally inherited molecule. The remaining 70 are nuclear encoded. This means that the mutations responsible for mitochondrial diseases may be inherited both in a mendelian and a maternal way. A group of the diseases caused by mutations in nuclear genes encoding proteins responsible for mtDNA maintenance is worth mentioning. mtDNA depletion or multiple deletions are observed as a result of such mutations. POLG and C10orf2 mutations are the most frequent in Polish patients. Next generation sequencing (NGS) enabled detailed analysis of both genomes. The application of NGS to mtDNA analysis in our hands has proven to be an effective tool to capture known as well as novel pathogenic variants. Due to the high number of reads and high coverage it also allows the detection of low levels of heteroplasmy. WES was applied to analyse genetic background of the disease in adult patients with progressive external ophthalmoplegia, multiple mtDNA deletions and negative screening for POLG and C10orf2 mutations. The preliminary results indicate that the success ratio is much lower than in paediatric patients. FINANCIAL SUPPORT: This work was supported by the National Science Center of Poland grant 2014/15/B/ NZ2/02272.

9

Nuclear genes involved in mitochondrial diseases with mitochondrial DNA instability in adults

52%

Rusecka J., Kierdaszuk B., Kaliszewska M., Rydzanicz M., Stawinski P., Gambin T., Kostera-Pruszczyk A., Bartnik E., Kaminska A., Ploski R., Tonska K.

Acta Biochimica Polonica

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2018

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tom 65

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nr S2

10

NGS as a diagnostic tool for unexplained limb-girdle muscles weakness: Results of European MYO-SEQ project in 75 Polish patients

46%

Lusakowska A., Johnson K., Topf A., Bertoli M., Phillips L., Straub V., Lek M., Xu L., MacArthur D. G., Macias A., Potulska-Chromik A., Kierdaszuk B., Janiszewska K., Arendt E., Grochowski P., Kaminska A., Kostera-Pruszczyk A.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

INTRODUCTION: Hereditary muscle disorders are a genetically heterogeneous group of rare diseases with overlapping phenotypes causing difficulties in establishing a diagnosis. Genetic testing isthe only reliable tool to confirm a prompt diagnosis.Genetically confirmed diagnosisisrequired forthe future targeted therapies and the genetic counselling. Department of Neurology, Warsaw Medical University, participated in a European multicenter project MYO‑SEQ led by Institute of Genetic Medicine, Newcastle University. AIM(S): The main aim of the project was to establish accurate diagnoses in patients with unexplained limb-girdle muscle weakness by applying New Generation Sequencing(NGS). MATERIAL Patients included in the study were at least 10 years old, presented with unexplained limb-girdle or respiratory muscle weakness and/or elevated serum CK activity. Based on these criteria we identified 75 patients treated at our Department of Neurology. METHOD(S): With the patients’ consent, their encoded DNA samples and anonymous clinical data were sent to the MYO‑SEQ coordinating center for a whole exome sequencing using NGS. A detailed analysis of potential mutations was restricted to 169 gene associated with neuromuscular disorders. When the molecular result were obtained, a detail clinical-genetic analysis was done. RESULTS: In total of 75 tested samples, 50 (66,7%) showed specific mutations responsible for the patients’ symptoms, including 45 (60,0%) with mutation in a single gene. In 5 samples (6,7%), mutations in more than one gene were found. In two patients the treatable diseases were identified: Pompe disease and congenital myasthenic syndrome. In 25 (33,3%) samples, no strong candidate gene was identified. CONCLUSIONS: NGS offers an accurate and reliable methodology to establish a diagnosis in rare inherited muscle diseases.When the new molecular therapies become available, NGS test should be included in a standard diagnostic procedure of myopathies.

Ograniczanie wyników

Hydroxylamine and methoxyamine mutagenesis: Tautomeric equilibrium of the promutagenic, N6-methoxyadenosine in solvents of different polarities

Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways

Chlorophyll-proteins complexes and photochemical activity of mesophyll and bundle sheath chloroplasts of C4 plants

Transformation of dimeric low-affinity form of human thymidine kinase [TK1] to the tetrameric high-affinity form [ATP-form]

Enantiospecificity of human deoxycytidine kinase [dCK] and thymidine kinases [TK1 and TK2] towards 3'-branched homologues of 2'-deoxynucleosides

Unusual nucleoside triphosphate donors for nucleoside kinases: 3'-deoxyadenosine-2'-triphosphate and 2'-deoxyadenosine-3'-triphosphate

Chronic progressive external ophthalmoplegia in Polish patients – clinical and genetic characteristics

Genetics of mitochondrial diseases – from mitochondrial DNA to whole exome studies

Nuclear genes involved in mitochondrial diseases with mitochondrial DNA instability in adults

NGS as a diagnostic tool for unexplained limb-girdle muscles weakness: Results of European MYO-SEQ project in 75 Polish patients