Role of Cellular DNA Repair Systems in HIV-1 Replication

2019 ◽  
Vol 53 (3) ◽  
pp. 313-322 ◽  
Author(s):  
A. N. Anisenko ◽  
M. B. Gottikh
Keyword(s):  
Dna Repair ◽  
Repair Systems ◽  
Cellular Dna ◽  
Hiv 1

Role of DNA repair systems in malignant tumor development in the elderly

2008 ◽  
Vol 8 (2) ◽  
pp. 65-72 ◽  
Author(s):  
Tomio Arai ◽  
Motoji Sawabe ◽  
Takayuki Hosoi ◽  
Noriko Tanaka
Keyword(s):  
Dna Repair ◽  
Malignant Tumor ◽  
Tumor Development ◽  
The Elderly ◽  
Repair Systems

Lipopolysaccharide (LPS) of Helicobacter modulates cellular DNA repair systems in intestinal cells

2010 ◽  
Vol 11 (3) ◽  
pp. 171-179 ◽  
Author(s):  
Pasqua Cavallo ◽  
Antonia Cianciulli ◽  
Vincenzo Mitolo ◽  
Maria Antonietta Panaro
Keyword(s):  
Dna Repair ◽  
Intestinal Cells ◽  
Repair Systems ◽  
Cellular Dna

scholarly journals NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase

Retrovirology ◽  
2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Ekaterina Knyazhanskaya ◽  
Andrey Anisenko ◽  
Olga Shadrina ◽  
Anastasia Kalinina ◽  
Timofei Zatsepin ◽  
...  
Keyword(s):  
Dna Repair ◽  
Wild Type Virus ◽  
Dna Breaks ◽  
End Joining ◽  
Double Stranded Dna ◽  
Repair Efficiency ◽  
Non Homologous End Joining ◽  
Cellular Dna ◽  
Successful Replication ◽  
Hiv 1

Abstract Background HIV-1 integration results in genomic DNA gaps that are repaired by cellular DNA repair pathways. This step of the lentiviral life cycle remains poorly understood despite its crucial importance for successful replication. We and others reported that Ku70 protein of the non-homologous end joining pathway (NHEJ) directly binds HIV-1 integrase (IN). Here, we studied the importance of this interaction for post-integrational gap repair and the recruitment of NHEJ factors in this process. Results We engineered HIV-based pseudovirus with mutant IN defective in Ku70 binding and generated heterozygous Ku70, Ku80 and DNA-PKcs human knockout (KO) cells using CRISPR/Cas9. KO of either of these proteins or inhibition of DNA-PKcs catalytic activity substantially decreased the infectivity of HIV-1 with native IN but not with the mutant one. We used a recently developed qPCR assay for the measurement of gap repair efficiency to show that HIV-1 with mutant IN was defective in DNA post-integrational repair, whereas the wild type virus displayed such a defect only when NHEJ system was disrupted in any way. This effect was present in CRISPR/Cas9 modified 293T cells, in Jurkat and CEM lymphoid lines and in primary human PBMCs. Conclusions Our data provide evidence that IN recruits DNA-PK to the site of HIV-1 post-integrational repair due to Ku70 binding—a novel finding that explains the involvement of DNA-PK despite the absence of free double stranded DNA breaks. In addition, our data clearly indicate the importance of interactions between HIV-1 IN and Ku70 in HIV-1 replication at the post-integrational repair step.

scholarly journals Role of variant allele fraction and rare SNP filtering to improve cellular DNA repair endpoint association

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206632 ◽  
Author(s):  
David M. Vossen ◽  
Caroline V. M. Verhagen ◽  
Reidar Grénman ◽  
Roelof J. C. Kluin ◽  
Marcel Verheij ◽  
...  
Keyword(s):  
Dna Repair ◽  
Variant Allele ◽  
Cellular Dna ◽  
Rare Snp ◽  
Variant Allele Fraction ◽  
Allele Fraction

The Role of the XPF Gene Polymorphism (Xrcc4) Ser835ser in the Risk of Malignant Transformation of Cells in the Colorectal Cancer

2015 ◽  
Vol 87 (2) ◽  
Author(s):  
Jacek Kabziński ◽  
Ireneusz Majsterek ◽  
Adam Dziki ◽  
Michał Mik
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Gene Polymorphism ◽  
Risk Groups ◽  
Control Group ◽  
Preventive Program ◽  
Increased Risk ◽  
Long Time ◽  
Repair Systems

AbstractParticipation of DNA repair systems in the pathogenesis of cancer has been a suspected phenomenon for a long time. Decreased efficiency in DNA repair translates to their ability to fix and consequently leads to mutations and the process of carcinogenesis. Linking individual polymorphisms of DNA repair systems with an increased risk of colorectal cancer will allow the classification of patients to high-risk groups and their placement under preventive program.The aim of the study was to determine the effect of XPF gene polymorphism Ser835Ser on increasing the risk of colorectal cancer in the Polish population.Material and methods. as the material blood collected from 146 patients diagnosed with colon cancer was used. The control group consisted of 149 healthy subjects. Genotyping was performed by Taq- Man method.Results. The results indicate that genotype TCC/TCT is associated with an decreased risk of colorectal cancer (OR 0.574; CI 95% 0.335-0.984; p=0.043).Conclusions. Based on these results, we conclude that the XPF gene polymorphism Ser835Ser may be associated with a decreased risk of colorectal cancer

Role of DNA Repair Systems Inhibition in Carcinogenicity of Metal Compounds

2005 ◽  
Vol 1 (3) ◽  
pp. 257-264
Author(s):  
D. Cavallo ◽  
C. Ursini ◽  
S. Iavicoli
Keyword(s):  
Dna Repair ◽  
Metal Compounds ◽  
Repair Systems

scholarly journals HIV-1 Vpr Reprograms CLR4DCAF1E3 Ubiquitin Ligase to Antagonize Exonuclease 1-Mediated Restriction of HIV-1 Infection

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Junpeng Yan ◽  
Ming-Chieh Shun ◽  
Caili Hao ◽  
Yi Zhang ◽  
Juan Qian ◽  
...  
Keyword(s):  
T Cells ◽  
Dna Repair ◽  
Accessory Protein ◽  
Dna Repair Enzymes ◽  
New Class ◽  
Repair Enzymes ◽  
Immunodeficiency Virus ◽  
Exonuclease 1 ◽  
Cellular Dna ◽  
Hiv 1

ABSTRACTViral accessory proteins hijack host cell E3 ubiquitin ligases to antagonize innate/intrinsic defenses and thereby provide a more permissive environment for virus replication. Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr reprograms CRL4DCAF1E3 to antagonize select postreplication DNA repair enzymes, but the significance and role of these Vpr interactions are poorly understood. To gain additional insights, we performed a focused screen for substrates of CRL4DCAF1E3 reprogrammed by HIV-1 Vpr among known postreplication DNA repair proteins and identified exonuclease 1 (Exo1) as a novel direct HIV-1 Vpr target. We show that HIV-1 Vpr recruits Exo1 to the CRL4DCAF1E3 complex for ubiquitination and subsequent proteasome-dependent degradation and that Exo1 levels are depleted in HIV-1-infected cells in a Vpr-dependent manner. We also show that Exo1 inhibits HIV-1 replication in T cells. Notably, the antagonism of Exo1 is a conserved function of main group HIV-1 and its ancestor Vpr proteins in the simian immunodeficiency virus from chimpanzee (SIVcpz) lineage, further underscoring the relevance of our findings. Overall, our studies (i) reveal that HIV-1 Vpr extensively remodels the cellular postreplication DNA repair machinery by impinging on multiple repair pathways, (ii) support a model in which Vpr promotes HIV-1 replication by antagonizing select DNA repair enzymes, and (iii) highlight the importance of a new class of restrictions placed on HIV-1 replication in T cells by the cellular DNA repair machinery.IMPORTANCEHIV-1 polymerase reverse transcribes the viral RNA genome into imperfectly double-stranded proviral DNA, containing gaps and flaps, for integration into the host cell chromosome. HIV-1 reverse transcripts share characteristics with cellular DNA replication intermediates and are thought to be converted into fully double-stranded DNA by cellular postreplication DNA repair enzymes. Therefore, the finding that the HIV-1 accessory protein Vpr antagonizes select postreplication DNA repair enzymes that can process HIV-1 reverse transcripts has been surprising. Here, we show that one such Vpr-antagonized enzyme, exonuclease 1, inhibits HIV-1 replication in T cells. We identify exonuclease 1 as a member of a new class of HIV-1 restriction factors in T cells and propose that certain modes of DNA “repair” inhibit HIV-1 infection.

The Role of DNA Repair Complex DNA-PK in HIV-1 Transcription

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 133
Author(s):  
Olga Shadrina ◽  
Andrey Anisenko ◽  
Marina Gottikh
Keyword(s):  
Dna Repair ◽  
Transcription Factors ◽  
Firefly Luciferase ◽  
Coding Region ◽  
Dna Breaks ◽  
Rnp Complex ◽  
The Impact ◽  
Hiv 1

The human DNA-dependent protein kinase (DNA-PK), composed of the heterodimeric protein Ku and catalytic subunit DNA-PKcs, is a sensor of double-strand DNA breaks in the non-homologous end-joining DNA repair pathway. The key role of DNA-PK in the post-integrational repair of HIV-1 has been shown. It has also been suggested that DNA-PK can participate in the regulation of HIV transcription, although the mechanism is unclear. To clarify the impact of each DNA-PK subunit on the transcription of HIV-1, HEK 293T cells, in which each of the DNA-PK components was depleted, were transfected with reporter vectors containing firefly luciferase under the control of HIV LTR promoter. We detected a positive influence of both Ku subunits, but not of DNA-PKcs, on the transcription from the HIV promoter. Ku is known to interact with HIV-1 TAR RNA, playing an essential role in viral transcription; nonetheless, the deletion of the TAR-coding region from LTR did not alter the Ku effect. Human small noncoding 7SK RNA participates in HIV-1 transcription. The direct binding of recombinant Ku and in vitro transcribed 7SK RNA was demonstrated using EMSA. In addition, we identified the interactions of endogenous Ku with proteins HEXIM1 and Cdk9 from the 7SK RNP complex. These results suggest that Ku exerts its effects on HIV-1 transcription via interaction with the 7SK RNP complex. However, we cannot rule out an indirect effect of Ku on transcription via the regulation of the levels of some transcription factors participating in HIV-1 transcription. We performed a transcriptome analysis of wild type HEK 293T cells and those with depleted DNA-PK subunits. The genes regulated by each subunit were defined and the genes that were mainly dependent on Ku subunits were selected. Among them, we identified transcription factors enhancing HIV-1 transcription, whose levels were downregulated in Ku-depleted cells. The study was supported by RFBR grant №18-04-00542 and RSF grant №17-14-01107.

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