scholarly journals The role of transposable elements and DNA damage repair mechanisms in gene amplification and protein domain shuffling in plant genomes

2019 ◽  
Author(s):  
Ksenia V Krasileva
Keyword(s):  
Dna Repair ◽  
Transposable Elements ◽  
Structural Variation ◽  
Gene Families ◽  
Protein Domain ◽  
Specific Gene ◽  
Chromosomal Dna ◽  
Plant Genomes ◽  
Gene Size ◽  
Repair Mechanisms

Plant genomes are shaped by structural variation. Gene-size insertions and among most prominent events and can have significant effects on amplification of gene families as well as facilitate new gene fusions. Transposable elements as well as plant DNA repair machinery have overlapping contributions to these events, and often work in synergy. Activity of transposable elements is often lineage specific and can preferentially affect specific gene families, such as disease resistance genes. Once duplicated, genes themselves can serve templates for additional variation that can arise from non-allelic homologous recombination. Non-homologous DNA repair mechanisms contribute to additional variation and diversify the mechanisms of gene movement, such as through ligation of extra-chromosomal DNA fragments. Genomic processes that generate structural variation can be induced by stress and therefore can provide adaptive potential. This review describes mechanisms that contribute to gene-size structural variation in plants, specifically gene duplication and generation of new plant genes through gene fusion.

scholarly journals The role of transposable elements and DNA damage repair mechanisms in gene amplification and protein domain shuffling in plant genomes

2019 ◽  
Author(s):  
Ksenia V Krasileva
Keyword(s):  
Dna Repair ◽  
Transposable Elements ◽  
Structural Variation ◽  
Gene Families ◽  
Protein Domain ◽  
Specific Gene ◽  
Chromosomal Dna ◽  
Plant Genomes ◽  
Gene Size ◽  
Repair Mechanisms

Plant genomes are shaped by structural variation. Gene-size insertions and among most prominent events and can have significant effects on amplification of gene families as well as facilitate new gene fusions. Transposable elements as well as plant DNA repair machinery have overlapping contributions to these events, and often work in synergy. Activity of transposable elements is often lineage specific and can preferentially affect specific gene families, such as disease resistance genes. Once duplicated, genes themselves can serve templates for additional variation that can arise from non-allelic homologous recombination. Non-homologous DNA repair mechanisms contribute to additional variation and diversify the mechanisms of gene movement, such as through ligation of extra-chromosomal DNA fragments. Genomic processes that generate structural variation can be induced by stress and therefore can provide adaptive potential. This review describes mechanisms that contribute to gene-size structural variation in plants, specifically gene duplication and generation of new plant genes through gene fusion.

scholarly journals Impact of transposable elements on methylation and gene expression across natural accessions of Brachypodium distachyon

2020 ◽  
Author(s):  
Michele Wyler ◽  
Christoph Stritt ◽  
Jean-Claude Walser ◽  
Célia Baroux ◽  
Anne C. Roulin
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transposable Elements ◽  
Plant Species ◽  
Brachypodium Distachyon ◽  
Expression Patterns ◽  
Small Subset ◽  
Molecular Evidence ◽  
Specific Gene ◽  
Plant Genomes

AbstractTransposable elements (TEs) constitute a large fraction of plant genomes and are mostly present in a transcriptionally silent state through repressive epigenetic modifications such as DNA methylation. TE silencing is believed to influence the regulation of adjacent genes, possibly as DNA methylation spreads away from the TE. Whether this is a general principle or a context-dependent phenomenon is still under debate, pressing for studying the relationship between TEs, DNA methylation and nearby gene expression in additional plant species. Here we used the grass Brachypodium distachyon as a model and produced DNA methylation and transcriptome profiles for eleven natural accessions. In contrast to what is observed in Arabidopsis thaliana, we found that TEs have a limited impact on methylation spreading and that only few TE families are associated to a low expression of their adjacent genes. Interestingly, we found that a subset of TE insertion polymorphisms is associated with differential gene expression across accessions. Thus, although not having a global impact on gene expression, distinct TE insertions may contribute to specific gene expression patterns in B. distachyon.Significance statementTransposable elements (TEs) are a major component of plant genomes and a source of genetic and epigenetic innovations underlying adaptation to changing environmental conditions. Yet molecular evidence linking TE silencing and nearby gene expression are lacking for many plant species. We show that in the model grass Brachypodium DNA methylation spreads over very short distances around TEs, with an influence on gene expression for a small subset of TE families.

scholarly journals Global and Local Manipulation of DNA Repair Mechanisms to Alter Site-Specific Gene Editing Outcomes in Hematopoietic Stem Cells

2020 ◽  
Vol 2 ◽  
Author(s):  
Elizabeth K. Benitez ◽  
Anastasia Lomova Kaufman ◽  
Lilibeth Cervantes ◽  
Danielle N. Clark ◽  
Paul G. Ayoub ◽  
...  
Keyword(s):  
Dna Repair ◽  
Gene Editing ◽  
Ex Vivo ◽  
Specific Gene ◽  
Gene Correction ◽  
End Joining ◽  
Therapeutic Success ◽  
Hematopoietic Stem ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms

Monogenic disorders of the blood system have the potential to be treated by autologous stem cell transplantation of ex vivo genetically modified hematopoietic stem and progenitor cells (HSPCs). The sgRNA/Cas9 system allows for precise modification of the genome at single nucleotide resolution. However, the system is reliant on endogenous cellular DNA repair mechanisms to mend a Cas9-induced double stranded break (DSB), either by the non-homologous end joining (NHEJ) pathway or by the cell-cycle regulated homology-directed repair (HDR) pathway. Here, we describe a panel of ectopically expressed DNA repair factors and Cas9 variants assessed for their ability to promote gene correction by HDR or inhibit gene disruption by NHEJ at the HBB locus. Although transient global overexpression of DNA repair factors did not improve the frequency of gene correction in primary HSPCs, localization of factors to the DSB by fusion to the Cas9 protein did alter repair outcomes toward microhomology-mediated end joining (MMEJ) repair, an HDR event. This strategy may be useful when predictable gene editing outcomes are imperative for therapeutic success.

scholarly journals GreenPhylDB v5: a comparative pangenomic database for plant genomes

2020 ◽  
Vol 49 (D1) ◽  
pp. D1464-D1471 ◽  
Author(s):  
Guignon Valentin ◽  
Toure Abdel ◽  
Droc Gaëtan ◽  
Dufayard Jean-François ◽  
Conte Matthieu ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Gene Families ◽  
Protein Domain ◽  
Global Food Security ◽  
Plant Genomes ◽  
Genomic Relationships ◽  
Genomic Studies ◽  
Tree Topologies ◽  
Community Curation ◽  
Orthology Detection

Abstract Comparative genomics is the analysis of genomic relationships among different species and serves as a significant base for evolutionary and functional genomic studies. GreenPhylDB (https://www.greenphyl.org) is a database designed to facilitate the exploration of gene families and homologous relationships among plant genomes, including staple crops critically important for global food security. GreenPhylDB is available since 2007, after the release of the Arabidopsis thaliana and Oryza sativa genomes and has undergone multiple releases. With the number of plant genomes currently available, it becomes challenging to select a single reference for comparative genomics studies but there is still a lack of databases taking advantage several genomes by species for orthology detection. GreenPhylDBv5 introduces the concept of comparative pangenomics by harnessing multiple genome sequences by species. We created 19 pangenes and processed them with other species still relying on one genome. In total, 46 plant species were considered to build gene families and predict their homologous relationships through phylogenetic-based analyses. In addition, since the previous publication, we rejuvenated the website and included a new set of original tools including protein-domain combination, tree topologies searches and a section for users to store their own results in order to support community curation efforts.

scholarly journals Exploiting DNA Endonucleases to Advance Mechanisms of DNA Repair

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 530
Author(s):  
Marlo K. Thompson ◽  
Robert W. Sobol ◽  
Aishwarya Prakash
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Gene Editing ◽  
Adaptive Immune System ◽  
Zinc Finger Nucleases ◽  
Specific Gene ◽  
Target Sequence ◽  
Transcription Activator ◽  
Low Cytotoxicity

The earliest methods of genome editing, such as zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALENs), utilize customizable DNA-binding motifs to target the genome at specific loci. While these approaches provided sequence-specific gene-editing capacity, the laborious process of designing and synthesizing recombinant nucleases to recognize a specific target sequence, combined with limited target choices and poor editing efficiency, ultimately minimized the broad utility of these systems. The discovery of clustered regularly interspaced short palindromic repeat sequences (CRISPR) in Escherichia coli dates to 1987, yet it was another 20 years before CRISPR and the CRISPR-associated (Cas) proteins were identified as part of the microbial adaptive immune system, by targeting phage DNA, to fight bacteriophage reinfection. By 2013, CRISPR/Cas9 systems had been engineered to allow gene editing in mammalian cells. The ease of design, low cytotoxicity, and increased efficiency have made CRISPR/Cas9 and its related systems the designer nucleases of choice for many. In this review, we discuss the various CRISPR systems and their broad utility in genome manipulation. We will explore how CRISPR-controlled modifications have advanced our understanding of the mechanisms of genome stability, using the modulation of DNA repair genes as examples.

scholarly journals Platinum Complexes in Colorectal Cancer and Other Solid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2073
Author(s):  
Beate Köberle ◽  
Sarah Schoch
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Platinum Complexes ◽  
Dna Lesions ◽  
Dna Damage Signaling ◽  
Repair Mechanisms ◽  
P53 Inactivation

Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy.

scholarly journals DNA Damage Response in Multiple Myeloma: The Role of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Takayuki Saitoh ◽  
Tsukasa Oda
Keyword(s):  
Multiple Myeloma ◽  
Dna Damage ◽  
Dna Repair ◽  
Tumor Microenvironment ◽  
Dna Damage Response ◽  
Genetic Instability ◽  
Dna Repair Mechanisms ◽  
Damage Response ◽  
Repair Mechanisms

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by genomic instability. MM cells present various forms of genetic instability, including chromosomal instability, microsatellite instability, and base-pair alterations, as well as changes in chromosome number. The tumor microenvironment and an abnormal DNA repair function affect genetic instability in this disease. In addition, states of the tumor microenvironment itself, such as inflammation and hypoxia, influence the DNA damage response, which includes DNA repair mechanisms, cell cycle checkpoints, and apoptotic pathways. Unrepaired DNA damage in tumor cells has been shown to exacerbate genomic instability and aberrant features that enable MM progression and drug resistance. This review provides an overview of the DNA repair pathways, with a special focus on their function in MM, and discusses the role of the tumor microenvironment in governing DNA repair mechanisms.

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