Papers by Mihai Ciubotaru
Journal of Immunology, Nov 1, 1995
PubMed, 1991
This new replicative model here explained is the result of the fact that, even if replication and... more This new replicative model here explained is the result of the fact that, even if replication and transcription are distinct events during the cell evolution, they are functionally correlated, being responsible both for the main features of the cell, and for hormones affinity, too. This model of replication suggests the spreading of replication, in both directions symmetrically from the origin site of each replicon, as well as a simultaneous replication of both DNA strands, despite the fact that one of them was until now called "lagging" strand. These two events are explained by initiation of each DNA catena with distinct RNA polymerase forms depending on the presence or absence of the sigma 70 recognition factor (or its beta gamma analogous eukaryotic factor). The arguments sustaining these events were gathered from many already known genetic studies, some of them being here supposed to new interpretations (for instance, the phi x 174, M13 phages replication models). The disposition of both DNA strands during replication allows the intervening of both RNA polymerase types only in RNA primer synthesis. However, other physical restrictive interactions suggested theoretically prevent the going on of RNA polymerases activity like they do during transcription. This is the main reason that determines the exposure of DNA conformational changes occurring in the replication. These explanations may bring a possible new light about the "mystery" of the phenomenon producing the "replicative eye" inside the double helical structure of DNA.
Journal of Molecular Biology, Dec 1, 1999
Journal of Biological Chemistry, Feb 1, 2003
Journal of Biomolecular Structure & Dynamics, 2000
Abstract The binding of proteins to specific DNA sequences plays a central role in the regulation... more Abstract The binding of proteins to specific DNA sequences plays a central role in the regulation of gene expression. Crucial to understanding how these proteins exert their effects is insight into the structure and flexibility of the protein-DNA complex. Over the past several years much has been learned about how the intimate contacts made between proteins and DNA enable proteins to recognize and bind with high specificity only to their cognate DNA binding sites. Studies conducted in our laboratory have shown that sequence-specific binding of DNA by proteins not only involves the close approach of amino acids and base pairs in the binding site, but also that base pairs not in contact with the protein affect binding and specificity through sequence-specific effects on DNA structure. The direct reading of the DNA sequence by proteins occurs by chemical complementarity between the interacting groups. Proper alignment of the interacting surfaces of functional groups on the protein and DNA molecules is crucial to the formation of stable and specific protein-DNA complexes. In many cases, the appropriate juxtaposition of the chemically complementary groups requires mutual adjustments in the structure of protein and DNA. Failure to do so can result in loss of affinity, loss of specificity or both. Together, the dimer interface and noncontacted bases within or adjacent to the binding site direct the structural complementarity between the functional groups on the protein and DNA.
Nucleic Acids Research, Dec 29, 2014
Molecular and Cellular Biology, Oct 1, 2004
The FASEB Journal, Apr 1, 2007
Scientific Reports, Jun 16, 2021
Immunology Letters, Dec 1, 1994
Journal of Biomolecular Structure & Dynamics, May 18, 2015
models of PCNAK107-Ub, PCNAK164-Ub and PCNAK164SUMO complexes consistent with solution small angl... more models of PCNAK107-Ub, PCNAK164-Ub and PCNAK164SUMO complexes consistent with solution small angle X-ray scattering (SAXS) data. We show that Ub and SUMO have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding conformations and the position of ubiquitin attachment, 107 vs. 164, alters conformation. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations. These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation.
Biochemistry, Apr 1, 2003
Typical of many transcriptional regulatory proteins, the lambdoid bacteriophage repressors bind c... more Typical of many transcriptional regulatory proteins, the lambdoid bacteriophage repressors bind cooperatively to multiple sites on DNA. This cooperative binding is essential for establishment and maintenance of phage lysogeny. In the phage, two repressor homodimers, one bound at each of the adjacent operator sites, interact to form the tetramer that is necessary for the cooperative binding of the repressor. Bacteriophage 434 repressor does not form tetramers in the absence of DNA, and the mechanism by which the tetramer assembles on the two adjacent sites is unknown. Hence DNA binding may stimulate the repressor to form tetramers and formation of a repressor oligomer (> or = 3 monomers) on a single DNA sites may precede multisite binding. Consistent with these ideas, a complex containing three repressor molecules readily assembles on a single operator (O(R)1) site. Mutations that inhibit cooperative tetramer binding to the adjacent O(R)1 and O(R)2 sites also block formation of this complex. Together with other evidence, these findings show that the complex that forms on a single site assembles using the same interface as does the tetramer assembled on adjacent operator sites. Adding additional O(R)1 DNA dissociates the oligomeric repressor-DNA complexes into dimeric repressor-O(R)1 complexes. In contrast, adding O(R)2 to these complexes results in the formation of a repressor oligomer containing an O(R)2 and an O(R)1 site. The observation that a repressor oligomer bound to two O(R)1 sites is less stable than the one formed between repressor dimers bound to O(R)1 and O(R)2 implies that DNA allosterically influences the structure of the 434 repressor. Together these findings suggest that an O(R)1-bound repressor may cooperatively help repressor bind to O(R)2 by recruiting an additional repressor molecule from solution that subsequently occupies O(R)2.
Molecular and Cellular Biology, Jul 1, 2007
Endocrinologie, 1991
This new replicative model here explained is the result of the fact that, even if replication and... more This new replicative model here explained is the result of the fact that, even if replication and transcription are distinct events during the cell evolution, they are functionally correlated, being responsible both for the main features of the cell, and for hormones affinity, too. This model of replication suggests the spreading of replication, in both directions symmetrically from the origin site of each replicon, as well as a simultaneous replication of both DNA strands, despite the fact that one of them was until now called "lagging" strand. These two events are explained by initiation of each DNA catena with distinct RNA polymerase forms depending on the presence or absence of the sigma 70 recognition factor (or its beta gamma analogous eukaryotic factor). The arguments sustaining these events were gathered from many already known genetic studies, some of them being here supposed to new interpretations (for instance, the phi x 174, M13 phages replication models). The ...
Planta medica international open, Oct 1, 2017
Molecular and Cellular Biology, 2007
Journal of Biomolecular Structure and Dynamics, 2000
Abstract The binding of proteins to specific DNA sequences plays a central role in the regulation... more Abstract The binding of proteins to specific DNA sequences plays a central role in the regulation of gene expression. Crucial to understanding how these proteins exert their effects is insight into the structure and flexibility of the protein-DNA complex. Over the past several years much has been learned about how the intimate contacts made between proteins and DNA enable proteins to recognize and bind with high specificity only to their cognate DNA binding sites. Studies conducted in our laboratory have shown that sequence-specific binding of DNA by proteins not only involves the close approach of amino acids and base pairs in the binding site, but also that base pairs not in contact with the protein affect binding and specificity through sequence-specific effects on DNA structure. The direct reading of the DNA sequence by proteins occurs by chemical complementarity between the interacting groups. Proper alignment of the interacting surfaces of functional groups on the protein and DNA molecules is crucial to the formation of stable and specific protein-DNA complexes. In many cases, the appropriate juxtaposition of the chemically complementary groups requires mutual adjustments in the structure of protein and DNA. Failure to do so can result in loss of affinity, loss of specificity or both. Together, the dimer interface and noncontacted bases within or adjacent to the binding site direct the structural complementarity between the functional groups on the protein and DNA.
Journal of Biological Chemistry, 2002
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Papers by Mihai Ciubotaru