Open Access
Retrovirology, volume 16, issue 1, publication number 30
NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase
Knyazhanskaya Ekaterina
1, 2, 3
,
Anisenko Andrey
1, 2
,
Shadrina Olga
4
,
Kalinina Anastasia
5
,
Zatsepin Timofei
1, 6
,
Zalevsky Arthur
4
,
Mazurov Dmitriy
7, 8
,
Gottikh Marina
1, 2
2
3
Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, USA
|
Publication type: Journal Article
Publication date: 2019-11-06
PubMed ID:
31690330
Infectious Diseases
Virology
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.
Citations by journals
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6
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International Journal of Molecular Sciences
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Frontiers in Cellular and Infection Microbiology
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1 publication, 4.35%
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Frontiers in Virology
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1 publication, 4.35%
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1 publication, 4.35%
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FEBS Journal
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FEBS Journal
1 publication, 4.35%
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Immunology
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1 publication, 4.35%
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Disease Markers
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1 publication, 4.35%
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Citations by publishers
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9
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Multidisciplinary Digital Publishing Institute (MDPI)
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9 publications, 39.13%
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Elsevier
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Elsevier
4 publications, 17.39%
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Frontiers Media S.A.
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Frontiers Media S.A.
2 publications, 8.7%
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Springer Nature
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Springer Nature
2 publications, 8.7%
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Public Library of Science (PLoS)
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2 publications, 8.7%
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Wiley
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Hindawi Limited
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1 publication, 4.35%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Knyazhanskaya E. et al. NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase // Retrovirology. 2019. Vol. 16. No. 1. 30
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Knyazhanskaya E., Anisenko A., Shadrina O., Kalinina A., Zatsepin T., Zalevsky A., Mazurov D., Gottikh M. NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase // Retrovirology. 2019. Vol. 16. No. 1. 30
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TY - JOUR
DO - 10.1186/s12977-019-0492-z
UR - https://doi.org/10.1186%2Fs12977-019-0492-z
TI - NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase
T2 - Retrovirology
AU - Knyazhanskaya, Ekaterina
AU - Anisenko, Andrey
AU - Shadrina, Olga
AU - Kalinina, Anastasia
AU - Zatsepin, Timofei
AU - Zalevsky, Arthur
AU - Mazurov, Dmitriy
AU - Gottikh, Marina
PY - 2019
DA - 2019/11/06 00:00:00
PB - Springer Nature
IS - 1
VL - 16
PMID - 31690330
SN - 1742-4690
ER -
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@article{2019_Knyazhanskaya,
author = {Ekaterina Knyazhanskaya and Andrey Anisenko and Olga Shadrina and Anastasia Kalinina and Timofei Zatsepin and Arthur Zalevsky and Dmitriy Mazurov and Marina Gottikh},
title = {NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase},
journal = {Retrovirology},
year = {2019},
volume = {16},
publisher = {Springer Nature},
month = {nov},
url = {https://doi.org/10.1186%2Fs12977-019-0492-z},
number = {1},
doi = {10.1186/s12977-019-0492-z}
}
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