Evidence that the Nijmegen breakage syndrome protein, an early sensor of double-strand DNA breaks (DSB), is involved in HIV-1 post-integration repair by recruiting the ataxia telangiectasia-mutated kinase in a process similar to, but distinct from, cellular DSB repair.

Virology Journal
Johanna A SmithRené Daniel

Abstract

Retroviral transduction involves integrase-dependent linkage of viral and host DNA that leaves an intermediate that requires post-integration repair (PIR). We and others proposed that PIR hijacks the host cell double-strand DNA break (DSB) repair pathways. Nevertheless, the geometry of retroviral DNA integration differs considerably from that of DSB repair and so the precise role of host-cell mechanisms in PIR remains unclear. In the current study, we found that the Nijmegen breakage syndrome 1 protein (NBS1), an early sensor of DSBs, associates with HIV-1 DNA, recruits the ataxia telangiectasia-mutated (ATM) kinase, promotes stable retroviral transduction, mediates efficient integration of viral DNA and blocks integrase-dependent apoptosis that can arise from unrepaired viral-host DNA linkages. Moreover, we demonstrate that the ATM kinase, recruited by NBS1, is itself required for efficient retroviral transduction. Surprisingly, recruitment of the ATR kinase, which in the context of DSB requires both NBS1 and ATM, proceeds independently of these two proteins. A model is proposed emphasizing similarities and differences between PIR and DSB repair. Differences between the pathways may eventually allow strategies to block PIR whi...Continue Reading

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Citations

Oct 26, 2010·Biotechnology Letters·Johanna A Smith, René Daniel
Apr 27, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Daiki TaneichiYukihito Ishizaka
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Feb 26, 2013·Retrovirology·Takayoshi KoyamaYukihito Ishizaka
Sep 18, 2010·Virology Journal·Johanna A SmithRené Daniel
Oct 27, 2010·PLoS Genetics·Ann DemoginesSara L Sawyer
Dec 25, 2013·Journal of Radiation Research·Masao S SasakiShunichi Takeda
Jan 12, 2016·Biomolecules·Ellis L RyanRoger J Grand
May 30, 2009·International Journal of Radiation Biology·Ping-Kun ZhouJing An
Jun 17, 2016·Bioinformatics·Siddhartha JainZiv Bar-Joseph
Aug 23, 2020·Cells·Andrey AnisenkoMarina Gottikh
Jul 12, 2014·BMC Evolutionary Biology·Dianne I LouSara L Sawyer

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Methods Mentioned

BETA
flow cytometry
Transfection
Immunoprecipitation
PCR
FACS
ChIP
immunoprecipitations

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