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71.
D. Yu. Khlimankov N. I. Rechkunova D. M. Kolpashchikov I. O. Petruseva S. N. Khodyreva A. Favre O. I. Lavrik 《Molecular Biology》2001,35(5):702-708
Replication protein A (RPA) is a heterotrimeric protein that has high affinity for single-stranded (ss) DNA and is involved in DNA replication, repair, and recombination in eukaryotic cells. Photoaffinity modification was employed in studying the interaction of human RPA with DNA duplexes containing various gaps, which are similar to structures arising during DNA replication and repair. A photoreactive dUMP derivative was added to the 3" end of a gap-flanking oligonucleotide with DNA polymerase , and an oligonucleotide containing a 5"-photoreactive group was chemically synthesized. The 5" end predominantly interacted with the large RPA subunit (p70) regardless of the gap size, whereas interactions of the 3" end with the RPA subunits depended both on the gap size and on the RPA concentration. Subunit p32 was mostly labeled in the case of a larger gap and a lower RPA concentration. The results confirmed the model of polar RPA–DNA interaction, which has been advanced earlier. 相似文献
72.
73.
Kolpashchikov DM Hughes P Favre A Baldacci G Lavrik OI 《Journal of molecular recognition : JMR》2001,14(4):239-244
Replication factor C (RFC) is a heteropentameric sliding clamp loader protein essential for processive synthesis of DNA by eukaryotic DNA polymerases delta and epsilon. To study the interaction of RFC with 3' and 5' ends of the DNA primer, we have developed chemical photocrosslinking assay using a synthetic DNA gap and DNA primer-template structures. We have found that the radioactively labeled primers containing a photoreactive group at their 5' end could crosslink with the largest RFC subunit (RFC140) on primer-templates and DNA gap structures, but that 3' end photoreactive primers could only crosslink with RFC140 within the DNA gap structure. Addition of replication protein A (RPA) to the reaction mixture resulted in the crosslinking of RPA subunits and inhibited crosslinking of RFC140 using 3' but not 5' photoreactive primers present at the gap. The results suggest specific contacts between RFC140 and the 5' end of the DNA primer. Together with previous data, these experiments allow us to propose a model for the DNA polymerase switch during eukaryotic DNA replication. 相似文献
74.
I S Bukhrashvili D Z Chinchaladze O I Lavrik A S Levina G A Nevinsky D A Prangishvili 《Biochimica et biophysica acta》1989,1008(1):102-107
Optimal conditions for polymerization reaction catalyzed on poly(dA) and poly(dT) templates by DNA polymerases from thermoacidophilic archaebacteria--DNA polymerase A from Sulfolobus acidocaldarius and DNA polymerase B from Thermoplasma acidophilum--have been established. Values of Km and Vmax (60 degrees C) for a set of primers d(pA)n and d(pT)n have been estimated. Minimal primers for both enzymes are dNMP. Lengthening of primers by each mononucleotide increases their affinity about 2.16-fold. Linear dependence of log Km and of log vmax on the number of mononucleotide links in primers (n) has breaking point at n = 10. The value of Vmax is about 20% of that for decanucleotide. The affinity of the primer d(pA)9p(rib*) with a deoxyribosylurea residue at the 3'-end does not differ essentially from that of d(pA)9. Substitution of the 3'-terminal nucleotide of a complementary primer for a noncomplementary nucleotide, e.g., substitution of 3'-terminal A for C in d(pA)10 in the reaction catalyzed on poly(dT), decreases the affinity of a primer by one order of magnitude. 相似文献
75.
76.
Dyrkheeva N. S. Zakharenko A. L. Novoselova E. S. Chepanova A. A. Popova N. A. Nikolin V. P. Luzina O. A. Salakhutdinov N. F. Ryabchikova E. I. Lavrik O. I. 《Molecular Biology》2021,55(2):273-277
Molecular Biology - Topotecan is a cytostatic drug from the camptothecin group, it acts by inhibiting topoisomerase 1 (TOP1). Tyrosyl-DNA phosphodiesterase 1 (TDP1) is capable of interfering with... 相似文献
77.
Kupryushkin M. S. Zharkov T. D. Ilina E. S. Markov O. V. Kochetkova A. S. Akhmetova M. M. Lomzov A. A. Pyshnyi D. V. Lavrik O. I. Khodyreva S. N. 《Russian Journal of Bioorganic Chemistry》2021,47(3):719-733
Russian Journal of Bioorganic Chemistry - In this work, representatives of the class of triazinylamidophosphate oligonucleotide derivatives were obtained for the first time. A scheme for the... 相似文献
78.
Shatnyeva OM Kubarenko AV Weber CE Pappa A Schwartz-Albiez R Weber AN Krammer PH Lavrik IN 《PloS one》2011,6(5):e19927
Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems. 相似文献
79.
Nucleotide excision repair (NER) is one of the major DNA repair pathways in eukaryotic cells counteracting genetic changes
caused by DNA damage. NER removes a wide set of structurally diverse lesions such as pyrimidine dimers arising upon UV irradiation
and bulky chemical adducts arising upon exposure to carcinogens or chemotherapeutic drugs. NER defects lead to severe diseases
including some forms of cancer. In view of the broad substrate specificity of NER, it is of interest to understand how a certain
set of proteins recognizes various DNA lesions in the context of a large excess of intact DNA. This review focuses on DNA
damage recognition and following stages resulting in preincision complex assembly, the key and still most unclear steps of
NER. The major models of primary damage recognition and preincision complex assembly are considered. The contribution of affinity
labeling techniques in study of this process is discussed. 相似文献
80.
Sonja Blasche Mario M?rtl Holger Steuber Gabriella Siszler Shahista Nisa Frank Schwarz Inna Lavrik Thomas M. A. Gronewold Klaus Maskos Michael S. Donnenberg Dirk Ullmann Peter Uetz Manfred K?gl 《PloS one》2013,8(3)
Enterohemorrhagic and enteropathogenic E. coli (EHEC and EPEC) can cause severe and potentially life-threatening infections. Their pathogenicity is mediated by at least 40 effector proteins which they inject into their host cells by a type-III secretion system leading to the subversion of several cellular pathways. However, the molecular function of several effectors remains unknown, even though they contribute to virulence. Here we show that one of them, NleF, binds to caspase-4, -8, and -9 in yeast two-hybrid, LUMIER, and direct interaction assays. NleF inhibits the catalytic activity of the caspases in vitro and in cell lysate and prevents apoptosis in HeLa and Caco-2 cells. We have solved the crystal structure of the caspase-9/NleF complex which shows that NleF uses a novel mode of caspase inhibition, involving the insertion of the carboxy-terminus of NleF into the active site of the protease. In conformance with our structural model, mutagenized NleF with truncated or elongated carboxy-termini revealed a complete loss in caspase binding and apoptosis inhibition. Evasion of apoptosis helps pathogenic E. coli and other pathogens to take over the host cell by counteracting the cell’s ability to self-destruct upon infection. Recently, two other effector proteins, namely NleD and NleH, were shown to interfere with apoptosis. Even though NleF is not the only effector protein capable of apoptosis inhibition, direct inhibition of caspases by bacterial effectors has not been reported to date. Also unique so far is its mode of inhibition that resembles the one obtained for synthetic peptide-type inhibitors and as such deviates substantially from previously reported caspase-9 inhibitors such as the BIR3 domain of XIAP. 相似文献