scholarly journals Genome Editing Strategies to Protect Livestock from Viral Infections

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1996
Author(s):  
Jenny-Helena Söllner ◽  
Thomas C. Mettenleiter ◽  
Björn Petersen
Keyword(s):  
Viral Infections ◽  
Disease Outbreaks ◽  
Transgenic Animals ◽  
Viral Disease ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Host Interactions ◽  
Associated Proteins ◽  
Preventive Vaccination ◽  
Control And Eradication

The livestock industry is constantly threatened by viral disease outbreaks, including infections with zoonotic potential. While preventive vaccination is frequently applied, disease control and eradication also depend on strict biosecurity measures. Clustered regularly interspaced palindromic repeats (CRISPR) and associated proteins (Cas) have been repurposed as genome editors to induce targeted double-strand breaks at almost any location in the genome. Thus, CRISPR/Cas genome editors can also be utilized to generate disease-resistant or resilient livestock, develop vaccines, and further understand virus–host interactions. Genes of interest in animals and viruses can be targeted to understand their functions during infection. Furthermore, transgenic animals expressing CRISPR/Cas can be generated to target the viral genome upon infection. Genetically modified livestock can thereby reduce disease outbreaks and decrease zoonotic threats.

scholarly journals Surveillance of Different Recombination Defects in Mouse Spermatocytes Yields Distinct Responses despite Elimination at an Identical Developmental Stage

2005 ◽  
Vol 25 (16) ◽  
pp. 7203-7215 ◽  
Author(s):  
Marco Barchi ◽  
Shantha Mahadevaiah ◽  
Monica Di Giacomo ◽  
Frédéric Baudat ◽  
Dirk G. de Rooij ◽  
...  
Keyword(s):  
Cellular Response ◽  
Stage Iv ◽  
Development Stage ◽  
Male Meiosis ◽  
Double Strand Breaks ◽  
Dsb Repair ◽  
Strand Breaks ◽  
Epistasis Analysis ◽  
Associated Proteins ◽  
Normal Males

ABSTRACT Fundamentally different recombination defects cause apoptosis of mouse spermatocytes at the same stage in development, stage IV of the seminiferous epithelium cycle, equivalent to mid-pachynema in normal males. To understand the cellular response(s) that triggers apoptosis, we examined markers of spermatocyte development in mice with different recombination defects. In Spo11 − / − mutants, which lack the double-strand breaks (DSBs) that initiate recombination, spermatocytes express markers of early to mid-pachynema, forming chromatin domains that contain sex body-associated proteins but that rarely encompass the sex chromosomes. Dmc1 − / − spermatocytes, impaired in DSB repair, appear to arrest at or about late zygonema. Epistasis analysis reveals that this earlier arrest is a response to unrepaired DSBs, and cytological analysis implicates the BRCT-containing checkpoint protein TOPBP1. Atm − / − spermatocytes show similarities to Dmc1 − / − spermatocytes, suggesting that ATM promotes meiotic DSB repair. Msh5 − / − mutants display a set of characteristics distinct from these other mutants. Thus, despite equivalent stages of spermatocyte elimination, different recombination-defective mutants manifest distinct responses, providing insight into surveillance mechanisms in male meiosis.

scholarly journals Suppression of telomere capping defects of Saccharomyces cerevisiae yku70 and yku80 mutants by telomerase

2021 ◽  
Author(s):  
Cory L Holland ◽  
Brian A Sanderson ◽  
James K Titus ◽  
Monica F Weis ◽  
Angelica M Riojas ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Double Strand Breaks ◽  
Temperature Sensitive ◽  
Chromosomal Dna ◽  
Strand Breaks ◽  
Growth Defects ◽  
Structural Reinforcement ◽  
Associated Proteins ◽  
Telomere Capping ◽  
Dna Ends

Abstract The Ku complex performs multiple functions inside eukaryotic cells, including protection of chromosomal DNA ends from degradation and fusion events, recruitment of telomerase, and repair of double-strand breaks (DSBs). Inactivation of Ku complex genes YKU70 or YKU80 in cells of the yeast S. cerevisiae gives rise to mutants that exhibit shortened telomeres and temperature-sensitive growth. In this study we have investigated the mechanism by which overexpression of telomerase suppresses the temperature sensitivity of yku mutants. Viability of yku cells was restored by overexpression of the Est2 reverse transcriptase and TLC1 RNA template subunits of telomerase, but not the Est1 or Est3 proteins. Overexpression of other telomerase- and telomere-associated proteins (Cdc13, Stn1, Ten1, Rif1, Rif2, Sir3, Sir4) did not suppress the growth defects of yku70 cells. Mechanistic features of suppression were assessed using several TLC1 RNA deletion derivatives and Est2 enzyme mutants. Supraphysiological levels of three catalytically inactive reverse transcriptase mutants (Est2-D530A, Est2-D670A and Est2-D671A) suppressed the loss of viability as efficiently as the wildtype Est2 protein, without inducing cell senescence. Roles of proteins regulating telomere length were also determined. The results support a model in which chromosomes in yku mutants are stabilized via a replication-independent mechanism involving structural reinforcement of protective telomere cap structures.

scholarly journals CRISPR-Cas adaptive immunity and the three Rs

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Tom Killelea ◽  
Edward L. Bolt
Keyword(s):  
Dna Replication ◽  
Adaptive Immunity ◽  
Trigger Points ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Associated Proteins ◽  
Fundamental Biology ◽  
The Three Rs ◽  
Cas Proteins

In this summary, we focus on fundamental biology of Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-Cas (CRISPR-associated proteins) adaptive immunity in bacteria. Emphasis is placed on emerging information about functional interplay between Cas proteins and proteins that remodel DNA during homologous recombination (HR), DNA replication or DNA repair. We highlight how replication forks may act as ‘trigger points’ for CRISPR adaptation events, and the potential for cascade-interference complexes to act as precise roadblocks in DNA replication by an invader MGE (mobile genetic element), without the need for DNA double-strand breaks.

The Diagnosis of Viral Disease by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 270-273
Author(s):  
William B. McCombs ◽  
Cameron E. McCoy
Keyword(s):  
Electron Microscopy ◽  
Hospital Stay ◽  
Viral Infections ◽  
Medical Profession ◽  
Bacterial Pathogens ◽  
Viral Disease ◽  
Viral Pathogens ◽  
Academic Interest ◽  
The Past

Recent years have brought a reversal in the attitude of the medical profession toward the diagnosis of viral infections. Identification of bacterial pathogens was formerly thought to be faster than identification of viral pathogens. Viral identification was dismissed as being of academic interest or for confirming the presence of an epidemic, because the patient would recover or die before this could be accomplished. In the past 10 years, the goal of virologists has been to present the clinician with a viral identification in a matter of hours. This fast diagnosis has the potential for shortening the patient's hospital stay and preventing the administering of toxic and/or expensive antibiotics of no benefit to the patient.

Repair pathway choice for double-strand breaks

2020 ◽  
Vol 64 (5) ◽  
pp. 765-777 ◽  
Author(s):  
Yixi Xu ◽  
Dongyi Xu
Keyword(s):  
Cell Cycle ◽  
Double Strand Breaks ◽  
Homologous Region ◽  
Gene Repair ◽  
Repair Pathway ◽  
Dna Double Strand Breaks ◽  
Environmental Radiation ◽  
Strand Breaks ◽  
Dna End Resection ◽  
End Resection

Abstract Deoxyribonucleic acid (DNA) is at a constant risk of damage from endogenous substances, environmental radiation, and chemical stressors. DNA double-strand breaks (DSBs) pose a significant threat to genomic integrity and cell survival. There are two major pathways for DSB repair: nonhomologous end-joining (NHEJ) and homologous recombination (HR). The extent of DNA end resection, which determines the length of the 3′ single-stranded DNA (ssDNA) overhang, is the primary factor that determines whether repair is carried out via NHEJ or HR. NHEJ, which does not require a 3′ ssDNA tail, occurs throughout the cell cycle. 53BP1 and the cofactors PTIP or RIF1-shieldin protect the broken DNA end, inhibit long-range end resection and thus promote NHEJ. In contrast, HR mainly occurs during the S/G2 phase and requires DNA end processing to create a 3′ tail that can invade a homologous region, ensuring faithful gene repair. BRCA1 and the cofactors CtIP, EXO1, BLM/DNA2, and the MRE11–RAD50–NBS1 (MRN) complex promote DNA end resection and thus HR. DNA resection is influenced by the cell cycle, the chromatin environment, and the complexity of the DNA end break. Herein, we summarize the key factors involved in repair pathway selection for DSBs and discuss recent related publications.

Bestimmung der DNA-Schädigung in vitro

2010 ◽  
Vol 49 (S 01) ◽  
pp. S64-S68
Author(s):  
E. Dikomey
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Chromosome Aberrations ◽  
Genetic Factors ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Cell Inactivation ◽  
Repair Mechanisms ◽  
Break Repair

SummaryIonising irradiation acts primarily via induction of DNA damage, among which doublestrand breaks are the most important lesions. These lesions may lead to lethal chromosome aberrations, which are the main reason for cell inactivation. Double-strand breaks can be repaired by several different mechanisms. The regulation of these mechanisms appears be fairly different for normal and tumour cells. Among different cell lines capacity of doublestrand break repair varies by only few percents and is known to be determined mostly by genetic factors. Knowledge about doublestrand break repair mechanisms and their regulation is important for the optimal application of ionising irradiation in medicine.

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