Mechanisms Of 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.

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 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.

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.

Dna Damage Dna Repair And Disease

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Author : Miral Dizdaroglu
language : en
Publisher: Royal Society of Chemistry
Release Date : 2020-11-11

Dna Damage Dna Repair And Disease written by Miral Dizdaroglu and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-11-11 with Science categories.

The DNA of all organisms is constantly being damaged by endogenous and exogenous sources. Oxygen metabolism generates reactive species that can damage DNA, proteins and other organic compounds in living cells. Exogenous sources include ionizing and ultraviolet radiations, carcinogenic compounds and environmental toxins among others. The discovery of multiple DNA lesions and DNA repair mechanisms showed the involvement of DNA damage and DNA repair in the pathogenesis of many human diseases, most notably cancer. These books provide a comprehensive overview of the interdisciplinary area of DNA damage and DNA repair, and their relevance to disease pathology. Edited by recognised leaders in the field, this two-volume set is an appealing resource to a variety of readers including chemists, chemical biologists, geneticists, cancer researchers and drug discovery scientists.

Mechanisms Of Dna Repair

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Author :
language : en
Publisher: Academic Press
Release Date : 2012-10-22

Mechanisms Of Dna Repair written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-10-22 with Science categories.

Written by research experts, this volume of Progress in Molecular Biology and Translational Science focuses on current science surrounding the mechanisms of DNA repair. Contributions from leading authorities Informs and updates on all the latest developments in the field

Dna Repair And Replication

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Author : Roger J. A. Grand
language : en
Publisher: Garland Science
Release Date : 2018-09-03

Dna Repair And Replication written by Roger J. A. Grand and has been published by Garland Science this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-09-03 with Science categories.

DNA Repair and Replication brings together contributions from active researchers. The first part of this book covers most aspects of the DNA damage response, emphasizing the relationship to replication stress. The second part concentrates on the relevance of this to human disease, with particular focus on both the causes and treatments which make use of DNA Damage Repair (DDR) pathways. Key Selling Features: Chapters written by leading researchers Includes description of replication processes, causes of damage, and methods of repair

Dna Repair Mechanisms

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Author : ICN Pharmaceuticals, inc
language : en
Publisher:
Release Date : 1978

Dna Repair Mechanisms written by ICN Pharmaceuticals, inc and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1978 with Science categories.

DNA Repair Mechanisms is an account of the proceedings at a major international conference on DNA Repair Mechanisms held at Keystone, Colorado on February 1978. The conference discusses through plenary sessions the overall standpoint of DNA repair. The papers presented and other important documents, such as short summaries by the workshop session conveners, comprise this book. The compilation describes the opposing views, those that agree and dispute about certain topic areas. This book, divided into 15 parts, is arranged according to the proceedings in the conference. The plenary sessions are ...

Molecular Mechanisms For Repair Of Dna

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Author : Philip Hanawalt
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06

Molecular Mechanisms For Repair Of Dna written by Philip Hanawalt 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.

An "age" has passed in the 40 years since we first observed recovery from radiation damage in irradiated bacteria. During the early 1930s, we had been discussing the possibility of rapid changes after radiation exposure with Farring ton Daniels, Benjamin Duggar, John Curtis, and others at the University of Wisconsin. After working with living cells, we had concluded that organisms receiving massive insults must have a wide variety of repair mechanisms available for restoration of at least some of the essential properties of the cell. The problem was how to fmd and identify these recovery phenomena. At that time I was working on a problem considered to be of great importance-the existence of the so-called mitogenetic rays. Several hundred articles and a score of books had already appeared dealing with mitogenetic rays, a type of radiation that was thought to exist in the shorter ultraviolet region. Our search for mitogenetic rays necessitated the design of experiments of greatest sensitivity for the detection of ultraviolet. It was vital that conditions be kept as constant as possible during exposure. All the work was done at icewater temperature (3-5°C) during and after exposure. We knew that light was an important factor for cell recovery, so all our experiments were done in dim light, with the plated-out cells being covered with dark cloth. Our statements on the effect of visible light stimulated Kelner to search for "photoreactivation' (as it was later called).