Maintenance of Genome Integrity: DNA Damage Sensing, Signaling, Repair and Replication in Plants


Book Description

Environmental stresses and metabolic by-products can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. As a consequence, plant growth and productivity are irreversibly compromised. To overcome genotoxic injury, plants have evolved complex strategies relying on a highly efficient repair machinery that responds to sophisticated damage perception/signaling networks. The DNA damage signaling network contains several key components: DNA damage sensors, signal transducers, mediators, and effectors. Most of these components are common to other eukaryotes but some features are unique to the plant kingdom. ATM and ATR are well-conserved members of PIKK family, which amplify and transduce signals to downstream effectors. ATM primarily responds to DNA double strand breaks while ATR responds to various forms of DNA damage. The signals from the activated transducer kinases are transmitted to the downstream cell-cycle regulators, such as CHK1, CHK2, and p53 in many eukaryotes. However, plants have no homologue of CHK1, CHK2 nor p53. The finding of Arabidopsis transcription factor SOG1 that seems functionally but not structurally similar to p53 suggests that plants have developed unique cell cycle regulation mechanism. The double strand break repair, recombination repair, postreplication repair, and lesion bypass, have been investigated in several plants. The DNA double strand break, a most critical damage for organisms are repaired non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Damage on template DNA makes replication stall, which is processed by translesion synthesis (TLS) or error-free postreplication repair (PPR) pathway. Deletion of the error-prone TLS polymerase reduces mutation frequencies, suggesting PPR maintains the stalled replication fork when TLS is not available. Unveiling the regulation networks among these multiple pathways would be the next challenge to be completed. Some intriguing issues have been disclosed such as the cross-talk between DNA repair, senescence and pathogen response and the involvement of non-coding RNAs in global genome stability. Several studies have highlighted the essential contribution of chromatin remodeling in DNA repair DNA damage sensing, signaling and repair have been investigated in relation to environmental stresses, seed quality issues, mutation breeding in both model and crop plants and all these studies strengthen the idea that components of the plant response to genotoxic stress might represent tools to improve stress tolerance and field performance. This focus issue gives researchers the opportunity to gather and interact by providing Mini-Reviews, Commentaries, Opinions, Original Research and Method articles which describe the most recent advances and future perspectives in the field of DNA damage sensing, signaling and repair in plants. A comprehensive overview of the current progresses dealing with the genotoxic stress response in plants will be provided looking at cellular and molecular level with multidisciplinary approaches. This will hopefully bring together valuable information for both plant biotechnologists and breeders.




Maintenance of Genome Integrity: DNA Damage Sensing, Signaling, Repair and Replication in Plants


Book Description

Environmental stresses and metabolic by-products can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. As a consequence, plant growth and productivity are irreversibly compromised. To overcome genotoxic injury, plants have evolved complex strategies relying on a highly efficient repair machinery that responds to sophisticated damage perception/signaling networks. The DNA damage signaling network contains several key components: DNA damage sensors, signal transducers, mediators, and effectors. Most of these components are common to other eukaryotes but some features are unique to the plant kingdom. ATM and ATR are well-conserved members of PIKK family, which amplify and transduce signals to downstream effectors. ATM primarily responds to DNA double strand breaks while ATR responds to various forms of DNA damage. The signals from the activated transducer kinases are transmitted to the downstream cell-cycle regulators, such as CHK1, CHK2, and p53 in many eukaryotes. However, plants have no homologue of CHK1, CHK2 nor p53. The finding of Arabidopsis transcription factor SOG1 that seems functionally but not structurally similar to p53 suggests that plants have developed unique cell cycle regulation mechanism. The double strand break repair, recombination repair, postreplication repair, and lesion bypass, have been investigated in several plants. The DNA double strand break, a most critical damage for organisms are repaired non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Damage on template DNA makes replication stall, which is processed by translesion synthesis (TLS) or error-free postreplication repair (PPR) pathway. Deletion of the error-prone TLS polymerase reduces mutation frequencies, suggesting PPR maintains the stalled replication fork when TLS is not available. Unveiling the regulation networks among these multiple pathways would be the next challenge to be completed. Some intriguing issues have been disclosed such as the cross-talk between DNA repair, senescence and pathogen response and the involvement of non-coding RNAs in global genome stability. Several studies have highlighted the essential contribution of chromatin remodeling in DNA repair. DNA damage sensing, signaling and repair have been investigated in relation to environmental stresses, seed quality issues, mutation breeding in both model and crop plants and all these studies strengthen the idea that components of the plant response to genotoxic stress might represent tools to improve stress tolerance and field performance. This focus issue gives researchers the opportunity to gather and interact by providing Mini-Reviews, Commentaries, Opinions, Original Research and Method articles which describe the most recent advances and future perspectives in the field of DNA damage sensing, signaling and repair in plants. A comprehensive overview of the current progresses dealing with the genotoxic stress response in plants will be provided looking at cellular and molecular level with multidisciplinary approaches. This will hopefully bring together valuable information for both plant biotechnologists and breeders.




DNA Repair and Replication


Book Description

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




Grappling with the Multifaceted World of the DNA Damage Response


Book Description

DNA damage is a major threat to genomic integrity and cell survival. It can arise both spontaneously and in response to exogenous agents. DNA damage can attack most parts of the DNA structure, ranging from minor and major chemical modifications, to single-strand breaks (SSBs) and gaps, to full double-strand breaks (DSBs). If DNA injuries are mis-repaired or unrepaired, they may ultimately result in mutations or wider-scale genome aberrations that threaten cell homeostasis. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. This Research Topic was aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes.




DNA Repair, Part B


Book Description

This volume emphasizes the intracellular consequences of DNA damage, describing procedures for analysis of checkpoint responses, DNA repair in vivo, replication fork encounter of DNA damage, as well as biological methods for analysis of mutation production and chromosome rearrangements. It also describes molecular methods for analysis of a number of genome maintenance activities including DNA ligases, helicases, and single-strand binding proteins.*Part B of a 2-part series*Addresses DNA maintenance enzymes*Discusses damage signaling*Presents In vivo analysis of DNA repair*Covers mutation and chromosome rearrangements




DNA Repair


Book Description

The preservation of expected life span and longevity, as well as the assurance of life succession among all species requires the integrity and faithful transcription of DNA. A dedicated machinery of DNA repair factors is responsible for reversing DNA damage across the genome. Efficient response to various effectors of DNA damage is also dependent on a complex network of sensors and mediators of stress signals which are upstream of DNA repair activation and together constitute components of the DNA damage response (DDR). This book reviews research on cell cycle checkpoints as essential mechanisms for safeguarding genome stability; nucleotide excision repair (NER) which recognises and removes bulky DNA damage that leads to DNA double-helix distortion and others.




DNA Repair and Replication


Book Description

DNA Repair and Replication contains an up-to-date review of general principles of DNA replication and an overview of the multiple pathways involved in DNA repair. Specific DNA repair pathways, including base-excision repair, light-dependent direct reversal of UV-damage, nucleotide-excision repair, transcription-coupled repair, double-strand break repair, and mismatch repair, are each discussed in separate chapters.Selected Contents: - Base Excision Repair - Eukaryotic DNA Mismatch Repair - Double Strand Break Repair - Functions of DNA Polymerases - Somatic Hypermutation: A Mutational Panacea




DNA Repair


Book Description




DNA REPLICATION IN PLANTS


Book Description

This texts discusses DNA replication in plants including chapters on; functional chromosomal structure, the biochemistry of DNA replication, Control of DNA replication, Replication of plant organelle DNA, replication of DNA viruses in plants, and DNA damage, repair, and mutagenesis.




New Mechanisms Involved in the DNA Replication Stress Response of Non-transformed Human Cells


Book Description

The cell cycle, the group of processes involved in the duplication and division of a cell in two daughter cells is essential for all organism existence. The correct regulation of these processes is crucial to guarantee genome integrity and cell survival. From the different cell cycle phases, the S phase is the most vulnerable to the acquisition of DNA damage since it is the phase in which the DNA is replicated. Alterations in DNA replication dynamics result in the accumulation of replication stress, one of the major sources of genomic instability, a hallmark of cancer. In this sense, cells have developed complex surveillance mechanisms to ensure stabilization and repair of forks, to coordinate these functions with cell cycle, and thus, to prevent cell division in the presence of unreplicated or damaged DNA. By doing so, these mechanisms will try to overcome the damage, and if so, the DNA replication stress response will promote replication resumption. By contrast, in the cases of persistent damage, cells are withdrawal from the cell cycle either by apoptosis or senescence. The correct activation and regulation of all these mechanisms is essential to prevent the acquisition of genomic instability and the oncogenic transformation. The pathways involved in DNA damage detection and signaling have been extensively studied in tumor cells. However, the response to replication stress, especially in non-transformed human cells, is still poorly understood. Therefore, in order to gain a better understanding of the pathways involved in this response, the main objective of this thesis has been to study and characterize new mechanisms involved in the DNA replication stress response of non-transformed human cells, as well as to analyze their contribution towards safeguarding genome integrity. Combining cellular and molecular approaches, together with several replication stress inducing agents, we have characterized new DNA replication stress response mechanisms that prevent replication resumption upon severe replication stress. For instance, we have described that APC/CCdh1 ubiquitin ligase is prematurely activated in S phase, to prevent new origin firing, in response to a prolonged DNA replication inhibition that results in the processing of replication forks into double strand breaks. Additionally, using an approach that has allowed us to define the changes at replication fork level between an acute and prolonged replication stress, we have seen that replication forks suffer several remodeling and processing events that abrogate their ability to restart after severe replication stress. Notably, our results suggest that this loss in the ability to resume replication under these conditions may act as a mechanism to safeguard genome integrity in non-transformed human cells. Collectively, the results of this thesis contribute to have a better understanding of the mechanisms involved in the DNA replication stress response of non-transformed human cells, opening new doors for the development of future therapies.