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The Single-Stranded DNA Binding Protein of Bacteriophage T4
Published in James F. Kane, Multifunctional Proteins: Catalytic/Structural and Regulatory, 2019
Daniel H. Doherty, Peter Gauss, Larry Gold
We first note the effect of gp32 on a simple replication system that uses partially single-stranded lambda DNA (generated by exoIII digestion) as template and only one other protein of the T4 replication system, DNA polymerase.19 In this system (which mimics lagging-strand synthesis), gp32 stimulated DNA synthesis by the T4 DNA polymerase five to ten fold. Stimulation was greatest at low temperature and/or high salt concentration, conditions that favor intramolecular secondary structure in the template. The stimulation was interpreted as resulting from the removal of secondary structures present in the DNA template. However, denaturation of intramolecular structures is not sufficient to stimulate heterologous polymerases. The T4 single-stranded DNA binding protein does not stimulate E. coli DNA polymerase II but the E. coli single-stranded DNA binding protein (ssb gene product) does.58 This suggests that each DNA polymerase prefers single-stranded DNA with a conformation imposed by its homologous single-stranded DNA binding protein. The different contour lengths for DNA-protein bound complexes with gp32 and ssb (4.6A/nucleotide26 compared to 1.8A/nucleotide58) might reflect the base distortion required by the homologous polymerases for maximal stimulation of DNA synthesis in vitro (and perhaps in vivo). These results might also suggest that the stimulation of homologous polymerases is the result of direct protein-protein interactions between polymerase and single-stranded DNA binding protein. Such an interaction has been observed between gp32 and T4 DNA polymerase19,59 (and see below). However, we note that protein-protein complexes have not been observed betwen the T7 DNA polymerase and T7 DNA binding protein.60
LDB1-mediated transcriptional complexes are sensitive to islet stress
Published in Islets, 2022
Yanping Liu, Jessica D. Kepple, Anath Shalev, Chad S. Hunter
Our lab and others have shown that the LIM-homeodomain transcription factor, Islet-1 (ISL1), and interacting co-regulator, LIM domain-binding protein 1 (LDB1), are required for β-cell development and function.17–20 Comparative tissue- and cell-type-specific knockout mouse models revealed that LDB1:ISL1-containing complexes are necessary for β-cell development, identity, survival, and insulin secretory function via direct regulation of several key β-cell gene targets, including MafA, Pdx1, Slc2a2, Glp1r, among others.17–20 Previously published work from our lab utilizing in vitro protein interaction screens revealed the Single-Stranded DNA-Binding protein 3 (SSBP3, also called SSDP121,22) co-regulator participates in β-cell LDB1:ISL1 complexes and contributes to the regulation of MafA expression in β-cells.23 Further, ISL1 and LDB1 are maintained in human islets,19,20 highlighting the conservation and importance of these factors to mammalian β-cells and glucose homeostasis. However, little is known of whether the expression and/or interactions of ISL1 and LDB1 are modulated by β-cell stimuli or stressors.
Misconnecting the dots: altered mitochondrial protein-protein interactions and their role in neurodegenerative disorders
Published in Expert Review of Proteomics, 2020
Mara Zilocchi, Mohamed Taha Moutaoufik, Matthew Jessulat, Sadhna Phanse, Khaled A. Aly, Mohan Babu
Mt biogenesis and mitophagy are two additional mt endeavors that control mt mass and functions, and alterations of this process are also involved in NDs [3,11,23]. First, mt biogenesis implies the division of preexisting organelles through the classical trio of mtDNA replication, transcription and translation. This process accommodates increased energy demands in various brain tissues, and reports show plummeting mt biogenesis with age [98]. The DNA polymerase γ (POLG) acts together with other replisome components, such as TWINKLE mtDNA helicase (also known as PEO1), mt single-stranded DNA-binding protein (mtSSB) and mt DNA ligase III to initiate the replication of mtDNA [99]. ER-mt contact sites that are spatially linked to a subset of nucleoids and marked selectively by mtDNA polymerase are engaged with mtDNA replication and division to distribute newly replicated mtDNA in human cells, suggesting a functional interdependence between mt-ER dynamics and mt genome maintenance [79].
AID Biology: A pathological and clinical perspective
Published in International Reviews of Immunology, 2018
Meenal Choudhary, Anubhav Tamrakar, Amit Kumar Singh, Monika Jain, Ankit Jaiswal, Prashant Kodgire
Numerous cofactors related to AID have been identified that govern the target specificity of AID. The germinal center-associated nuclear protein (GANP) that is induced in germinal center B-cells during the immune response transports AID to the nucleus and assists in recruiting AID to actively transcribing IgV genes during SHM [76]. Replication protein A (RPA) is a highly conserved single-stranded DNA-binding protein in eukaryotes which plays an essential role in DNA replication and downstream DNA recombination and repair pathways [77]. RPA associated with the single-stranded DNA template undergoing transcription mediates access of the deaminase enzyme to its DNA substrate [78]. Vuong and co-researchers have shown that the interaction between AID and RPA is mediated by PKA that phosphorylates AID at the serine residue (S38) [79]. AID targets RNA Polymerase II stalled sites in DNA through its association with Spt5 [80]. Spt5-depletion impaired AID-polII interaction and diminished AID-recruitment to its Ig switch regions and non-Ig genes. Genome-wide ChIP-seq studies identified that regions with high Spt5 levels corresponded with sites of elevated AID localization and that genomic enrichment of Spt5 at stalled polII sites are an indication of AID-mediated mutations [80]. The essential role of SR-proteins in the immune response is also reported, where a splice isoform of SRSF1 (SRSF1-3) acts as a cofactor in inducing hypermutation at IgV genes in DT40 cells [81]. Albeit precise mechanisms governing AID targeting to immunoglobulin genes are yet to be resolved, several studies state about factors contributing to its specific recruitment to target DNA.