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DNA Repair Jan 2022The genomic DNA is constantly under attack by cellular and/or environmental factors. Fortunately, the cell is armed to safeguard its genome by various mechanisms such as... (Review)
Review
The genomic DNA is constantly under attack by cellular and/or environmental factors. Fortunately, the cell is armed to safeguard its genome by various mechanisms such as nucleotide excision, base excision, mismatch and DNA double-strand break repairs. While these processes maintain the integrity of the genome throughout, DNA repair occurs preferentially faster at the transcriptionally active genes. Such transcription-coupled repair phenomenon plays important roles to maintain active genome integrity, failure of which would interfere with transcription, leading to an altered gene expression (and hence cellular pathologies/diseases). Among the various DNA damages, DNA double-strand breaks are quite toxic to the cells. If DNA double-strand break occurs at the active gene, it would interfere with transcription/gene expression, thus threatening cellular viability. Such DNA double-strand breaks are found to be repaired faster at the active gene in comparison to its inactive state or the inactive gene, thus supporting the existence of a new phenomenon of transcription-coupled DNA double-strand break repair. Here, we describe the advances of this repair process.
Topics: DNA; DNA Breaks, Double-Stranded; DNA End-Joining Repair; DNA Repair; Eukaryota; Humans; Recombinational DNA Repair; Transcription, Genetic
PubMed: 34883263
DOI: 10.1016/j.dnarep.2021.103211 -
Methods in Molecular Biology (Clifton,... 2019Remarkable progress in the development of technologies for sequence-specific modification of primary DNA sequences has enabled the precise engineering of crops with... (Review)
Review
Remarkable progress in the development of technologies for sequence-specific modification of primary DNA sequences has enabled the precise engineering of crops with novel characteristics. These programmable sequence-specific modifiers include site-directed nucleases (SDNs) and base editors (BEs). Currently, these genome editing machineries can be targeted to specific chromosomal locations to induce sequence changes. However, the sequence mutation outcomes are often greatly influenced by the type of DNA damage being generated, the status of host DNA repair machinery, and the presence and structure of DNA repair donor molecule. The outcome of sequence modification from repair of DNA double-strand breaks (DSBs) is often uncontrollable, resulting in unpredictable sequence insertions or deletions of various sizes. For base editing, the precision of intended edits is much higher, but the efficiency can vary greatly depending on the type of BE used or the activity of the endogenous DNA repair systems. This article will briefly review the possible DNA repair pathways present in the plant cells commonly used for generating edited variants for genome engineering applications. We will discuss the potential use of DNA repair mechanisms for developing and improving methodologies to enhance genome engineering efficiency and to direct DNA repair processes toward the desired outcomes.
Topics: DNA Breaks, Double-Stranded; DNA End-Joining Repair; DNA Repair; DNA, Plant; Gene Editing; Genetic Engineering; Genome, Plant
PubMed: 30610624
DOI: 10.1007/978-1-4939-8991-1_1 -
Experimental Cell Research Aug 2021DNA damage is a constant stressor to the cell. Persistent damage to the DNA over time results in an increased risk of mutation and an accumulation of mutations with age.... (Review)
Review
DNA damage is a constant stressor to the cell. Persistent damage to the DNA over time results in an increased risk of mutation and an accumulation of mutations with age. Loss of efficient DNA damage repair can lead to accelerated ageing phenotypes or an increased cancer risk, and the trade-off between cancer susceptibility and longevity is often driven by the cell's response to DNA damage. High levels of mutations in DNA repair mutants often leads to excessive cell death and stem cell exhaustion which may promote premature ageing. Stem cells themselves have distinct characteristics that enable them to retain low mutation rates. However, when mutations do arise, stem cell clonal expansion can also contribute to age-related tissue dysfunction as well as heightened cancer risk. In this review, we will highlight increasing DNA damage and mutation accumulation as hallmarks common to both ageing and cancer. We will propose that anti-ageing interventions might be cancer preventative and discuss the mechanisms through which they may act.
Topics: Aging; DNA Damage; DNA Repair; Genomic Instability; Longevity; Neoplasms
PubMed: 34102225
DOI: 10.1016/j.yexcr.2021.112679 -
BioEssays : News and Reviews in... May 2018The repair of chromosomal double-strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the... (Review)
Review
The repair of chromosomal double-strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51-mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms. See also the video abstract here: https://youtu.be/vm7-X5uIzS8.
Topics: Animals; DNA Breaks, Double-Stranded; DNA Repair; Humans; Rad51 Recombinase; Rec A Recombinases; Recombinational DNA Repair
PubMed: 29603285
DOI: 10.1002/bies.201700229 -
Nature Oct 2009The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults... (Review)
Review
The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.
Topics: Cell Cycle; DNA Damage; DNA Repair; Disease; Genome, Human; Humans; Signal Transduction
PubMed: 19847258
DOI: 10.1038/nature08467 -
FEMS Microbiology Reviews Jul 2018There has long been a fascination in the DNA repair pathways of archaea, for two main reasons. Firstly, many archaea inhabit extreme environments where the rate of... (Review)
Review
There has long been a fascination in the DNA repair pathways of archaea, for two main reasons. Firstly, many archaea inhabit extreme environments where the rate of physical damage to DNA is accelerated. These archaea might reasonably be expected to have particularly robust or novel DNA repair pathways to cope with this. Secondly, the archaea have long been understood to be a lineage distinct from the bacteria, and to share a close relationship with the eukarya, particularly in their information processing systems. Recent discoveries suggest the eukarya arose from within the archaeal domain, and in particular from lineages related to the TACK superphylum and Lokiarchaea. Thus, archaeal DNA repair proteins and pathways can represent a useful model system. This review focuses on recent advances in our understanding of archaeal DNA repair processes including base excision repair, nucleotide excision repair, mismatch repair and double-strand break repair. These advances are discussed in the context of the emerging picture of the evolution and relationship of the three domains of life.
Topics: Archaea; Biological Evolution; DNA Repair; DNA, Archaeal
PubMed: 29741625
DOI: 10.1093/femsre/fuy020 -
Chemical Research in Toxicology 1989
Review
Topics: Animals; DNA Damage; DNA Repair; Humans; Nucleotides; Recombination, Genetic
PubMed: 2519777
DOI: 10.1021/tx00010a001 -
International Journal of Molecular... Jun 2018
Topics: Animals; DNA Damage; DNA Repair; DNA Replication; Disease; Genome, Human; Humans; Phosphorylation
PubMed: 29958460
DOI: 10.3390/ijms19071902 -
Molecules (Basel, Switzerland) May 2020Epigenetic research has rapidly evolved into a dynamic field of genome biology. Chromatin regulation has been proved to be an essential aspect for all genomic processes,... (Review)
Review
Epigenetic research has rapidly evolved into a dynamic field of genome biology. Chromatin regulation has been proved to be an essential aspect for all genomic processes, including DNA repair. Chromatin structure is modified by enzymes and factors that deposit, erase, and interact with epigenetic marks such as DNA and histone modifications, as well as by complexes that remodel nucleosomes. In this review we discuss recent advances on how the chromatin state is modulated during this multi-step process of damage recognition, signaling, and repair. Moreover, we examine how chromatin is regulated when different pathways of DNA repair are utilized. Furthermore, we review additional modes of regulation of DNA repair, such as through the role of global and localized chromatin states in maintaining expression of DNA repair genes, as well as through the activity of epigenetic enzymes on non-nucleosome substrates. Finally, we discuss current and future applications of the mechanistic interplays between chromatin regulation and DNA repair in the context cancer treatment.
Topics: Chromatin Assembly and Disassembly; DNA Damage; DNA Repair; Epigenesis, Genetic; Humans
PubMed: 32471288
DOI: 10.3390/molecules25112496 -
Environmental and Molecular Mutagenesis Apr 2024Deletions associated with the repair of DNA double-strand breaks is a source of genetic alternation and a recognized source of disease-causing mutagenesis.... (Review)
Review
Deletions associated with the repair of DNA double-strand breaks is a source of genetic alternation and a recognized source of disease-causing mutagenesis. Theta-mediated end joining is a DNA repair mechanism, which guarantees deletions by its employment of microhomology (MH) alignment to facilitate end joining. A lesser-characterized templated insertion ability of this pathway, on the other hand, is associated with both deletion and insertion. This mechanism is characterized by at least one round of polymerase θ-mediated synthesis, which does not result in successful repair, followed by a subsequent round of polymerase engagement and synthesis that does lead to repair. Here we focus on the mechanisms by which polymerase θ introduces these insertions-direct, inverse, and a new class which we have termed strand switching. We observe this new class of templated insertions at multiple loci and across multiple species, often at a comparable frequency to those previously characterized. Templated insertion mutations are often enriched in cancer genomes and repeat expansion disorders. This repair mechanism thus contributes to disease-associated mutagenesis, and may plausibly even promote disease. Characterization of the types of polymerase θ-dependent insertions can provide new insight into these diseases and clinical promise for treatment.
Topics: DNA End-Joining Repair; DNA Repair; DNA Breaks, Double-Stranded
PubMed: 37438951
DOI: 10.1002/em.22564