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Genome Editing for Genetic Lung Diseases
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Zinc-finger nucleases (ZFNs) were discovered as one of the first useful tools for genome editing.3,26 A zinc-finger protein (ZFP) is composed of at least three zinc-finger domains, which provide sequence specificity by recognizing 3-bp DNA sequence through each domain.3,26 To create ZFN, ZFP is fused with the non-specific cleavage domain of the FokI endonuclease.3,26 A pair of ZFNs generate DSBs of DNA with the dimerization of the cleavage domain.3,26 In past decades, the editing efficiency of ZFNs has been significantly enhanced, and the engineering process has been considerably improved.3 However, sophisticated protein engineering is still required to target new genomic sequences.3 Later on, another powerful genome editing platform named transcription activator-like effector nucleases (TALENs) were developed.27 Each monomer of the DNA binding domain recognizes one specific nucleotide of the target sequence.27 The simplicity of one monomer-one nucleotide rule allows a faster design and assembly process of TALENs than ZFNs.27,28
NAC in Abiotic Stresses
Published in Hasanuzzaman Mirza, Nahar Kamrun, Fujita Masayuki, Oku Hirosuke, Tofazzal M. Islam, Approaches for Enhancing Abiotic Stress Tolerance in Plants, 2019
Sami Ullah Jan, Muhammad Jamil, Muhammad Faraz Bhatti, Alvina Gul
DNA-binding domains are the primary sites for DNA–protein interactions. The part of transcription factor that has a conserved structural motif with capability to bind specific promoter or enhancer-sequence in a gene is called DNA-binding domain while, alternatively, the position/site on DNA where a transcription factor binds refers to Transcription Factor Binding Site (TFBS) or Response Element (RE) (Reid et al. , 2010). DBDs show more conserved pattern as compared to the other structural motifs (Atkinson and Urwin, 2012; Guo et al., 2005). DBDs are the key sites in determining the specificity, type and rate of binding a transcription factor to specific loci in DNA (Reid et al., 2010). These are highly organized folded-motifs with a variable number of amino acids, such as 50 in MYB-type TFs, 60 in WRKY-Type TFs (Liu et al., 2013), while 150–160 in NAC (Ooka et al., 2003).
Understanding the Technologies Involved in Gene Therapy
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Manish P. Patel, Jayvadan K. Patel, Mukesh Patel, Govind Vyas
Research was carried out on bacterial plant pathogen Xanthomonads which causes diseases on many plants a by Hrp-type III secretion (T3S) system. This secretion system is key in the translocation of effector proteins inside plant cells. It was also noted that the effector has a wide role in supporting bacterial virulence, multiplication and distribution. AvrBs3 or transcription activator-like (TAL) localized on pXV11 group (h2) genes were found in a significant amount in Xanthomonas spp. As the name suggests, TAL activates transcription in the cell nucleus. The binding specificity is determined by a modular DNA-binding domain (Boch et al. 2010).
Computational prediction models for assessing endocrine disrupting potential of chemicals
Published in Journal of Environmental Science and Health, Part C, 2018
Sugunadevi Sakkiah, Wenjing Guo, Bohu Pan, Rebecca Kusko, Weida Tong, Huixiao Hong
EDCs, mimic the natural hormones, are exogenous substances interacting with various proteins in the endocrine system and alter endocrine functions including metabolism, development, secretion, reproductive, and transport.1 Hormones bind with the proteins to produce signals which are essential to activate or depress the physiological functions of the protein. EDCs disrupt the endocrine system through various mechanisms by binding with other normally functioning proteins causing2–4: (i) elevation or depression of signal strength; (ii) inhibition of signal; or (iii) alteration of hormone synthesis and metabolism. Most EDCs interact with nuclear receptors. Nuclear receptors are ligand-dependent transcriptional factors that play a major role in reproduction, homeostatic, metabolism, transport, and more. The nuclear receptor superfamily is divided into three classes5,6: (i) steroid receptor family including glucocorticoid receptor, androgen receptor (AR), estrogen receptor (ER), and progesterone receptor; (ii) thyroid/retinoid family including vitamin D receptor, peroxisome proliferation-activated receptor, thyroid receptor and retinoic acid receptor; and (iii) nuclear receptors. A nuclear receptor is a single polypeptide chain that contains three major domains: (i) amino terminal domain, (ii) highly conserved DNA binding domain, and (iii) C-terminal or ligand binding domain.7 The DNA binding domain is a highly conserved domain and contains a DNA binding-specific motif that helps the formation of homo- or hetero-dimerization.8 The linker region, present between the DNA binding domain and Ligand binding domain, is a flexible region and contains a nuclear localization signal. The LBD contains a transcriptional activation function 2 and facilitates interaction with the chromatin remodeling and transcriptional activation functions.