Interaction of HMG proteins and H1 with hybrid PNA–DNA junctions

Totsingan, Filbert; Bell, Amanda

doi:10.1002/pro.2342

Cited by 13 publications

(6 citation statements)

References 70 publications

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“…The interaction between HMGB1 and linker histones (H1 and H5) occurs through their acidic and basic tails, respectively (Cato et al, 2008). This interaction between HMGB1 and H1 facilitates DNA-protein complex formation (Totsingan and Bell, 2013), DNA ligation reactions (Yamanaka et al, 2002) and enables stress-induced gene silencing (e.g., pro-inflammatory cytokine TNF-α) (El Gazzar et al, 2009). The interaction between HMGB1 and H1 is regulated by pH, local ionic concentration, and redox state (Kohlstaedt and Cole, 1994b; Kohlstaedt et al, 1987).…”

Section: Hmgb1 Functionmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

801

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Section: Hmgb1 Functionmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

801

828

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“…In our previous study, EMSAs were used to measure the binding constants of 4WJ-PNA 1 and 4WJ-PNA 3 toward HMGB1b. This report showed that the protein binds 4WJ-PNA 3 with a nearly identical affinity to J1 (K D ~ 6.0 μM) and 4WJ-PNA 1 slightly less (K D ~ 16.0 μM) 18 . Moreover, these data show that the insertion of a PNA strand into the immobilized lattice of J1 does not abolish protein recognition.…”

Section: Resultsmentioning

confidence: 75%

“…Three hybrids, 4WJ-PNA 1 , 4WJ-PNA 3 and 4WJ-PNA 1,3 , contain shorter PNA strands relative to the DNA strands (12 vs. 16) in order to minimize synthetic problems associated with longer PNA sequences (Figure 2A). In our previous study we show that the DNA overhangs, present in 4WJ-PNA 1 and 4WJ-PNA 3 , do not prohibit the formation of immobilized junctions because the non-bonded regions are not located close to the junction branch point 18 . To avoid overhanging DNA residues, three hybrids were designed with shorter (blunt) DNA strands: b 4WJ-PNA 1 , b 4WJ-PNA 3 and b 4WJ-PNA 1,3 .…”

Section: Introductionmentioning

confidence: 91%

“…We recently expanded upon the PNA-protein targeting strategy by designing hybrid PNA-DNA four-way junctions (4WJs) that bind the DNA-binding proteins, High Mobility Group B1b (HMGB1b) and Histone H1 18 . Four-way junctions are immobile versions of Holliday junctions, key intermediates in homologous and site-specific genetic recombination 19–21 .…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the structural and protein recognition properties of hybrid PNA–DNA four-way junctions

Iverson

Serrano

Brahan

et al. 2015

Archives of Biochemistry and Biophysics

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The objective of this study is to evaluate the structure and protein recognition properties of hybrid four-way junctions (4WJs) composed of DNA and peptide nucleic acid (PNA) strands. We compare a classic immobile DNA junction, J1, vs. six PNA-DNA junctions, including a number with blunt DNA ends and multiple PNA strands. Circular dichroism (CD) analysis reveals that hybrid 4WJs are composed of helices that possess structures intermediate between A- and B-form DNA, the apparent level of A-form structure correlates with the PNA content. The structure of hybrids that contain one PNA strand is sensitive to Mg+2. For these constructs, the apparent B-form structure and conformational stability (Tm) increase in high Mg+2. The blunt-ended junction, b4WJ-PNA3, possesses the highest B-form CD signals and Tm (40.1°C) values vs. all hybrids and J1. Protein recognition studies are carried out using the recombinant DNA-binding protein, HMGB1b. HMGB1b binds the blunt ended single-PNA hybrids, b4WJ-PNA1 and b4WJ-PNA3, with high affinity. HMGB1b binds the multi-PNA hybrids, 4WJ-PNA1,3 and b4WJ-PNA1,3, but does not form stable protein-nucleic acid complexes. Protein interactions with hybrid 4WJs are influenced by the ratio of A- to B-form helices: hybrids with helices composed of higher levels of B-form structure preferentially associate with HMGB1b.

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“…The data are based on the protocol used by Kallenbach and Seaman to characterize, J1 [2] , [3] . In our previous study, each hybrid PNA–DNA 4WJ is evaluated vs. J1 [4] .…”

Section: Datamentioning

confidence: 99%

Supporting data for the characterization of PNA–DNA four-way junctions

et al. 2015

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Holliday or DNA four-way junctions (4WJs) are cruciform/bent structures composed of four DNA duplexes. 4WJs are key intermediates in homologous genetic recombination and double-strand break repair. To investigate 4WJs in vitro, junctions are assembled using four asymmetric DNA strands. The presence of four asymmetric strands about the junction branch point eliminates branch migration, and effectively immobilizes the resulting 4WJ. The purpose of these experiments is to show that immobile 4WJs composed of DNA and peptide nucleic acids (PNAs) can be distinguished from contaminating labile nucleic acid structures. These data compare the electrophoretic mobility of hybrid PNA–DNA junctions vs. i) a classic immobile DNA 4WJ, J1 and ii) contaminating nucleic acid structures.

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Interaction of HMG proteins and H1 with hybrid PNA–DNA junctions

Cited by 13 publications

References 70 publications

HMGB1 in health and disease

HMGB1 in health and disease

Characterization of the structural and protein recognition properties of hybrid PNA–DNA four-way junctions

Supporting data for the characterization of PNA–DNA four-way junctions

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