Rna Damage And Repair
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Rna Damage And Repair
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Author : Ioly Kotta-Loizou
language : en
Publisher: Springer Nature
Release Date : 2021-07-04
Rna Damage And Repair written by Ioly Kotta-Loizou and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-07-04 with Science categories.
Ribonucleic acid (RNA) is a macromolecule that plays a central role in cell physiology: RNA molecules act as intermediates between the deoxyribonucleic acid (DNA), where genetic information is stored, and proteins, which perform the necessary functions within the cell. Traditionally, the structural and functional properties of RNA are closely linked to gene expression. However, RNA-based enzymes, called ribozymes, are also involved in catalysis and small RNAs regulate key cellular processes, such as cell growth, division, differentiation, aging and death. RNA is a sensitive macromolecule that can be easily damaged by environmental conditions (ultraviolet radiation, oxidative stress) and biological factors (ribonucleases, ribotoxins, CRISPR-Cas systems). Therefore, cells have developed mechanisms to protect and/or repair RNA molecules. This book presents an overview of the biology of RNA damage, protection and repair in prokaryotes and eukaryotes. Individual chapters cover the expression regulation, enzymology and physiological role of such systems, and link them to important human diseases such as cancer and degenerative diseases.
Mechanisms Of Rna Damage And Repair
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Author : Anupam K. Chakravarty
language : en
Publisher:
Release Date : 2014
Mechanisms Of Rna Damage And Repair written by Anupam K. Chakravarty and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Polynucleotide ligases preserve the integrity of the 3'-5' phosphodiester backbone in DNA and RNA -- a crucial aspect in the life cycle of any organism. This thesis explores various mechanisms that are employed during RNA damage and repair. Cyclic phosphates are key species in cellular RNA damage and repair pathways. Mechanistically, there are two distinct enzymatic routes to generate 2',3'-cyclic phosphate ends - transesterification and de novo cyclization using ATP. In this work, I have investigated reaction pathways that generate and utilize these cyclic phosphate ends in the context of RNA damage and repair. Specifically, I have studied cyclic-phosphate generation by RtcA ( E. coli Rtc homolog) and PaT (a eukaryal anticodon nuclease) from a structure-function perspective as well as cyclic-phosphate utilization by RtcB, a recently discovered RNA ligase. I trapped and crystallized E. coli RtcA at discrete stages of the reaction pathway. Crystal structures of RtcA*ATP binary complex, RtcA*ATP*metal ternary complex and an RtcA*AMP product complex were solved. These structural snapshots helped reconstruct the covalent adenylylation of RtcA at atomic resolution. The key findings from the study illustrated: i) metal induced reorganization of the phosphates of ATP to place the pyrophosphate leaving group apical to the active site histidine for an inline nucleophilic attack, ii) metal is not required for steps 2 & 3 of cyclization, later confirmed by biochemical assays, iii) molecular roles of conserved residues in the RtcA active site were assigned. I was also able to demonstrate the ligase-like capability of RtcA to adenylylate 5'-monophosphate ends of DNA and RNA. In E. coli and several other bacteria, rtcA is part of an operon with rtcB - a gene encoding for a protein whose function was unknown until 2011. RtcB was found to be a bona-fide tRNA ligase in vitro and in vivo . Using biochemical and mass spectrometric methods, I tested the veracity of the proposed d̀irect' ligation mechanism of RtcB. By isolating intermediates at discrete stages in the reaction pathway, I discovered that the 2',3'-cyclic phosphate/5'-hydroxyl ligation catalyzed by RtcB is not direct and entails - (i) reaction of His337 with GTP to form a covalent RtcB-(histidinyl-N)-GMP intermediate; (ii) hydrolysis of the 2',3'-cyclic phosphate to a 3'-phosphate (iii) transfer of guanylate to a RNA 3'-phosphate to form RNAppG intermediate; (iv) attack of 5'-hydroxyl moiety on the -RNAppG end to form the sealed phosphodiester. RtcB catalyzed RNA ligation is the first known example of a polynucleotide ligase that works via 3'-end activation. It raises the possibility of an alternative enzymology based on 3'-activated ends in nucleic acids. Fungal anticodon nucleases (ACNases) are toxins that cause growth arrest of foreign species by cleaving a single phosphodiester bond in the anticodon stem loop of specific tRNAs. Any structure function analysis on ACNases has so far evaded us for two reasons: 1) these toxins are sui generis and lack similarity in primary structure to any known nucleases, 2) there are no known three dimensional structures of any eukaryal ACNase. To that end, I crystallized and solved the structure of an ACNase from Pichia acaciae at 1.8 [Angstrom] resolution. The structure of Pichia acaciae toxin (PaT) reveals a novel three-dimensional fold with unique topology. Further, using an in vivo yeast growth arrest assay and an in vitro anticodon stem-loop cleavage assay, I have been able to define the enzyme active site, and elucidate the mechanism of action of this unique class of RNA damage proteins.
Biochemical And Structural Studies Of Rna Damage And Repair In Bacteria
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Author : Amy Lynn Carruthers
language : en
Publisher:
Release Date : 2019
Biochemical And Structural Studies Of Rna Damage And Repair In Bacteria written by Amy Lynn Carruthers and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
Dna Damage And Repair
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Author : Jac A. Nickoloff
language : en
Publisher: Springer Science & Business Media
Release Date : 1998-08-12
Dna Damage And Repair written by Jac A. Nickoloff and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 1998-08-12 with Science categories.
Cutting edge reviews by leading researchers illuminate key aspects of DNA repair in mammalian systems and its relationship to human genetic disease and cancer. Major topics include UV and X-Ray repair, repair of chemical damage, recombinational repair, mismatch repair, transcription-repair coupling, and the role of DNA repair in disease prevention. Extensive up-to-date references and rigorous peer-review of each chapter make this volume definitive and bring it to the active frontiers of research.
Discovery And Characterization Of Novel Rna Repair Systems
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Author :
language : en
Publisher:
Release Date : 2015
Discovery And Characterization Of Novel Rna Repair Systems written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.
Advances In Dna Damage And Repair
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Author : Miral Dizdaroglu
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Advances In Dna Damage And Repair written by Miral Dizdaroglu and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Science categories.
In recent years the field of DNA repair has flourished due to new findings on DNA repair mechanisms and the molecular basis of cancer. This volume covers the most recent developments in this research field and contains contributions from scientists working in various fields.
Dna
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Author : Payam Behzadi
language : en
Publisher: BoD – Books on Demand
Release Date : 2021-05-19
Dna written by Payam Behzadi and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-05-19 with Medical categories.
DNA is the most important biomolecule ever discovered. Indeed, this molecule bears genetic information from one generation to another. In this regard, DNA bases have a key role in transferring genetic information and data safely. However, there are cellular, genetic, and environmental factors that may damage the different parts of DNA molecules. These damages may result in mutations and cell death. As such, several DNA repair mechanisms have evolved. Over three sections, this book examines many of these mechanisms.
Dna Damage Repair Genes And Noncoding Rna In High Grade Gliomas And Its Clinical Relevance
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Author : Bibha Choudhary
language : en
Publisher:
Release Date : 2019
Dna Damage Repair Genes And Noncoding Rna In High Grade Gliomas And Its Clinical Relevance written by Bibha Choudhary and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with Electronic books categories.
Gliomas are the most common malignant tumors originating from the glial cells in the central nervous system. Grades III and IV, considered high-grade gliomas occur at a lower incidence (1.5%) but have higher mortality. Several genomic alterations like IDH mutation, MGMT mutation, 1p19q Codeletion, and p53 mutations have been attributed to its pathogenicity. Recently, several noncoding RNAs have also been identified to alter the expression of crucial genes. Current chemotherapeutic drugs include temozolomide targeting hypermethylated MGMT, a DNA repair protein; or bevacizumab, which targets VEGF. This book chapter delves deeper into the DNA damage repair pathway including its correlation with survival and the regulation of these genes by noncoding RNAs. Novel therapeutic drugs being developed are also highlighted.
Molecular Biology Of The Cell
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Author : Bruce Alberts
language : en
Publisher:
Release Date : 2002
Molecular Biology Of The Cell written by Bruce Alberts and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Cytology categories.
Origin Of Dna Repair In The Rna World
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Author : Carol Bernstein
language : en
Publisher:
Release Date : 2019
Origin Of Dna Repair In The Rna World written by Carol Bernstein and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with Science categories.
The early history of life on Earth likely included a stage in which life existed as self-replicating protocells with single-stranded RNA (ssRNA) genomes. In this RNA world, genome damage from a variety of sources (spontaneous hydrolysis, UV, etc.) would have been a problem for survival. Selection pressure for dealing with genome damage would have led to adaptive strategies for mitigating the damage. In today,Äôs world, RNA viruses with ssRNA genomes are common, and these viruses similarly need to cope with genome damage. Thus ssRNA viruses can serve as models for understanding the early evolution of genome repair. As the ssRNA protocells in the early RNA world evolved, the RNA genome likely gave rise, through a series of evolutionary stages, to the double-stranded DNA (dsDNA) genome. In ssRNA to dsDNA evolution, genome repair processes also likely evolved to accommodate this transition. Some of the basic features of ssRNA genome repair appear to have been retained in descendants with dsDNA genomes. In particular, a type of strand-switching recombination occurs when ssRNA replication is blocked by a damage in the template strand. Elements of this process appear to have a central role in recombinational repair processes during meiosis and mitosis of descendant dsDNA organisms.